Synchrotron Services

The Hauptman-Woodward Medical Research Institute manages the Industrial Macromolecular Crystallography Association Collaborative Access Team beamline (IMCA-CAT) at the Advanced Photon Source. The beamline is designed for high-throughput high-quality single-crystal studies. Small-Angle X-ray scattering is also available as a service. The service provides security and confidentiality for proprietary samples and data. 

The IMCA-CAT beamline at the Advanced Photon Source provides:

  • Expert staff – Dr. Lisa Keefe directs IMCA-CAT with a scientific and technical staff that have been successfully working with industry and academia for decades.
  • State-of-the-art source – An undulator beam with positional feedback and microbeam capability.
  • State-of-the-art beamline – Actor Gen 4 continuous soak robot, Eiger2 X 9M detector, ALIO goniometer, and on-axis imaging.
  • Purpose-built facilities – Laboratory and office module adjacent to the beamline.
  • Processing and data transfer – Comprehensive software suite available and rapid secure data transfer.
  • Experienced – Over 20,000 structured determined annually
  • Confidentiality – The Center is a secured facility and no information will be publically disclosed without the express written permission of the investigator(s).
IMCA Logo

Industry researchers access IMCA-CAT for proprietary data collection through two mechanisms, subscription, and membership. This provides advance scheduling for guaranteed frequent access, rapid access within one week of request for beamtime, remote or onsite data collection, or mail-in services, and security and confidentiality for samples and data.

IMCA-CAT Subscription

IMCA Membership

Non-proprietary proposal access

Word cloud generated 2020-2018 beamline users publication titles.

IMCA-CAT

IMCA-CAT is a structural biology research facility for pharmaceutical drug discovery programs. It was established in 1992 by the Industrial Macromolecular Crystallization Association (comprising  AbbVie, Bristol-Myers Squibb, Janssen, Merck, Novartis, and Pfizer) to design, build, and operate a research facility at the Advanced Photon Source, a high-energy synchrotron X-ray source at Argonne National Laboratory. Today, IMCA-CAT operates a state-of-the-art insertion device beamline for confidential and proprietary macromolecular crystallography experiments. To meet the demands of the pharmaceutical industry, IMCA-CAT is optimized for high-throughput data acquisition, is committed to generating the highest quality X-ray diffraction data, provides reliable access for proprietary research, ensures maximum efficiency, and invests in the facility to remain at the technical forefront for pharmaceutical research in structural biology.

Discovery and lead optimization phases of drug development are accelerated with high-throughput data acquisition at IMCA-CAT. Automated sample mounting, diffraction rastering for high-precision sample centering, and shutterless continuous-rotation data collection distinguish IMCA-CAT as an outstanding research environment for confidential and proprietary structural biology programs in the pharmaceutical industry.

Structural studies of the most challenging complexes, including membrane proteins, small crystals, and radiation-sensitive samples, benefit from advanced beamline capabilities. Fragment screening high-throughput demands are met with fully automated and fast processes for data acquisition. On-the-fly structural analyses are enabled by high-speed, secure, and encrypted data transfer to off-site locations for integrating with company-based pipelines.

The IMCA-CAT facility is a state-of-the-art facility for proprietary drug discovery research. Intense focused beam, robotics for sample mounting, diffraction rastering and high-speed precision sample positioning, and shutterless continuous-rotation data collection enable the beamline to meet the throughput demands of the pharmaceutical industry. Experiment design capabilities include wavelength tunability for MAD and SAD experiments, selectable mini beam for optimum beam size, and collect-along-a-vector for overcoming sample degradation. Guaranteed, frequent, and routine access for proprietary data acquisition, whether on-site, remotely, or via mail-in, smoothly integrates with pharmaceutical drug design work flows.

Collect data on-site or remotely from your home laboratory, or utilize mail-in service. Pharmaceutical companies interested in conducting proprietary experiments are invited to inquire about the IMCA-CAT Subscription Program. General users interested in conducting non-proprietary experiments should apply via the APS User Program.

Beamline Capabilities

Beam

Energy : 6 – 20 keV
Flux: 7.7 x 10E12 ph/sec @ sample
Focus: 70 µm (H) x 30 µm (V)
Mini beam: 5, 10, 20, 50, 300 µm apertures
Attenuation: 0 – 100 % with Al filters
Stability: beam positional feedback

 

Detector

Detector: DECTRIS Eiger2 X 9M
Distance: 130 – 975 mm
2Theta: 0 – 15°
Framing rate: 100 Hz
Resolution Calculator

 

Experiment

Goniometer: ALIO (soc 1.2 µm)
Camera: on-axis visualizer
Fluorescence: Rontec X-Flash silicon drift detector (SDD)
Cryo: Oxford Instruments Cryogen
Modes: auto (unattended, queued jobs) or manual
Access: on-site, remote, mail-in

Automation

Robotics: ACTOR robot (Rigaku, GEN 4, continuous soak)
Capacity: 180 – 240 samples
Dewars: 3 (independently configurable), 5 pucks / dewar
Pucks: ACTOR pucks, Unipucks, ALS pucks
Centering: diffraction rastering with loop centering (auto or manual)

Samples

Pins: 18 mm; all metal base types

Loops:

  • Molecular Dimensions: LithoLoop (round or mesh)
  • MiTeGen: MicroLoop (regular style), MicroCrystal Mount
  • Hampton Research: CryoLoop

Acceptable but not compatible with auto centering: Molecular Dimensions: LithoLoop (elliptical), MiTeGen: MicroMount, MicroLoop E, MicroMesh, MicroGripper

 

Data

Storage: >60 TB
Processing: xds, autoPROC, mosflm, d*TREK
Analysis: crystallography software available
Transfer:

  • IBM Aspera (FASP) high-speed, encrypted
  • rsync
  • Globus

The IMCA-CAT Team

Lisa Keefe Ph.D.

IMCA-CAT Director and VP for Advancing Therapeutics

Anne M Mulichak Ph.D.

Macromolecular Crystallographer

Jesse Yoder Ph.D.

Macromolecular Crystallographer

Joe Digilio

Systems Administrator

Erica Duguid Ph.D.

Macromolecular Crystallographer

J Lewis Muir

Software Engineer

Eric Zoellner

Beamline Technician

Intern positions

 

The IMCA-CAT beamline offers summer intern positions in collaboration with the Hauptman-Woodward Medical Research Institute. 

Structures collected at IMCA-CAT

Thumbnails are shown from the Protein Data Bank with the accession code. Representative models of unique structures are given but depositions with multiple ligands are not shown. The publically deposited data represents a fraction of the beamline output. 

User publications with structures from IMCA-CAT data (word cloud from titles)

2021

 

  1. Development of BET inhibitors as potential treatments for cancer: A search for structural diversity. 7MCF. Hill, M.D., Fang, H., Tokarski, J., Fanslau, C., Haarhoff, Z., Huang, C., Kramer, M., Menard, K., Monereau, L., Morrison, J., Ranasinghe, A., Shields, E.E., Tye, C.K., Westhouse, R., Everlof, G., Sheriff, S., Yan, C., Marsilio, F., Zhang, L., Zvyaga, T., Lee, F., Gavai, A.V., Degnan, A.P. Bioorg Med Chem Lett : 128108-128108 (2021).
  2. Discovery and Optimization of DNA Gyrase and Topoisomerase IV Inhibitors with Potent Activity against Fluoroquinolone-Resistant Gram-Positive Bacteria. 7LHZ. Lapointe, G., Skepper, C.K., Holder, L.M., Armstrong, D., Bellamacina, C., Blais, J., Bussiere, D., Bian, J., Cepura, C., Chan, H., Dean, C.R., De Pascale, G., Dhumale, B., Fisher, L.M., Fulsunder, M., Kantariya, B., Kim, J., King, S., Kossy, L., Kulkarni, U., Lakshman, J., Leeds, J.A., Ling, X., Lvov, A., Ma, S., Malekar, S., McKenney, D., Mergo, W., Metzger, L., Mhaske, K., Moser, H.E., Mostafavi, M., Namballa, S., Noeske, J., Osborne, C., Patel, A., Patel, D., Patel, T., Piechon, P., Polyakov, V., Prajapati, K., Prosen, K.R., Reck, F., Richie, D.L., Sanderson, M.R., Satasia, S., Savani, B., Selvarajah, J., Sethuraman, V., Shu, W., Tashiro, K., Thompson, K.V., Vaarla, K., Vala, L., Veselkov, D.A., Vo, J., Vora, B., Wagner, T., Wedel, L., Williams, S.L., Yendluri, S., Yue, Q., Yifru, A., Zhang, Y., Rivkin, A.  J Med Chem 64: 6329-6357 (2021).
  3. Azatricyclic Inverse Agonists of RORgammat That Demonstrate Efficacy in Models of Rheumatoid Arthritis and Psoriasis. 7LUK. Liu, Q., Xiao, H.Y., Batt, D.G., Xiao, Z., Zhu, Y., Yang, M.G., Li, N., Yip, S., Li, P., Sun, D., Wu, D.R., Ruzanov, M., Sack, J.S., Weigelt, C.A., Wang, J., Li, S., Shuster, D.J., Xie, J.H., Song, Y., Sherry, T., Obermeier, M.T., Fura, A., Stefanski, K., Cornelius, G., Khandelwal, P., Dudhgaonkar, S., Rudra, A., Nagar, J., Murali, V., Govindarajan, A., Denton, R., Zhao, Q., Meanwell, N.A., Borzilleri, R.M., Dhar, T.G.M. ACS Med Chem Lett. (2021).
  4. Redefining the Histone Deacetylase Inhibitor Pharmacophore: High Potency with No Zinc Cofactor Interaction. 7LTL, 7LTK. Beshore, D.C., Adam, G.C., Barnard, R.J.O., Burlein, C., Gallicchio, S.N., Holloway, M.K., Krosky, D., Lemaire, W., Myers, R.W., Patel, S., Plotkin, M.A., Powell, D.A., Rada, V., Cox, C.D., Coleman, P.J., Klein, D.J., Wolkenberg, S.E. ACS Med Chem Lett 12: 540-547 (2021).
  5. Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET. 6WVZ. Neijssen, J., Cardoso, R.M.F., Chevalier, K.M., Wiegman, L., Valerius, T., Anderson, G.M., Moores, S.L., Schuurman, J., Parren, P.W.H.I., Strohl, W.R., Chiu, M.L. J Biol Chem : 100641-100641 (2021).
  6. Small molecule and macrocyclic pyrazole derived inhibitors of myeloperoxidase (MPO)  Bioorg Med Chem Lett 42: 128010-128010 (2021).7LAL, 7LAE. Hu, C.H., Neissel Valente, M.W., Halpern, O.S., Jusuf, S., Khan, J.A., Locke, G.A., Duke, G.J., Liu, X., Duclos, F.J., Wexler, R.R., Kick, E.K., Smallheer, J.M. Bioorg Med Chem Lett 42: 128010-128010 (2021).
  7. Expanding the repertoire for “large small molecules” : Prodrug ABBV-167 efficiently converts to venetoclax with reduced food effect in healthy volunteers. 7LHB. Salem, A.H., Tao, Z.F., Bueno, O.F., Chen, J., Chen, S., Edalji, R., Elmore, S.W., Fournier, K.M., Harper, K.C., Hong, R., Jenkins, G.J., Ji, J., Judge, R.A., Kalvass, J.C., Klix, R.C., Ku, Y.Y., Leverson, J.D., Marks, R.A., Marsh, K.C., Menon, R.M., Park, C.H., Phillips, D.C., Pu, Y.M., Rosenberg, S.H., Sanzgiri, Y.D., Sheikh, A.Y., Shi, Y., Stolarik, D., Suleiman, A.A., Wang, X., Zhang, G.G.Z., Catron, N.D., Souers, A.J. Mol Cancer Ther. (2021).
  8. Structure-activity relationship of ipglycermide binding to phosphoglycerate mutases. 7KNF. Wiedmann, M., Dranchak, P.K., Aitha, M., Queme, B., Collmus, C.D., Kashipathy, M.M., Kanter, L., Lamy, L., Rogers, J.M., Tao, D., Battaile, K.P., Rai, G., Lovell, S., Suga, H., Inglese, J.  J Biol Chem : 100628-100628 (2021).
  9. Combining random mutagenesis, structure-guided design and next-generation sequencing to mitigate polyreactivity of an anti-IL-21R antibody. 7KQ7. Campbell, S.M., DeBartolo, J., Apgar, J.R., Mosyak, L., McManus, V., Beyer, S., Bennett, E.M., Lambert, M., Cunningham, O. MAbs 13: 1883239-1883239 (2021).
  10. Structures of mouse and human GITR-GITRL complexes reveal unique TNF superfamily interactions. 7KHX, 7KHD. Wang, F., Chau, B., West, S.M., Kimberlin, C.R., Cao, F., Schwarz, F., Aguilar, B., Han, M., Morishige, W., Bee, C., Dollinger, G., Rajpal, A., Strop, P. Nat Commun 12: 1378-1378 (2021).
  11. Tricyclic-Carbocyclic ROR gamma t Inverse Agonists-Discovery of BMS-986313. 7KQJ. Yang, M.G., Beaudoin-Bertrand, M., Xiao, Z., Marcoux, D., Weigelt, C.A., Yip, S., Wu, D.R., Ruzanov, M., Sack, J.S., Wang, J., Yarde, M., Li, S., Shuster, D.J., Xie, J.H., Sherry, T., Obermeier, M.T., Fura, A., Stefanski, K., Cornelius, G., Khandelwal, P., Karmakar, A., Basha, M., Babu, V., Gupta, A.K., Mathur, A., Salter-Cid, L., Denton, R., Zhao, Q., Dhar, T.G.M.  J Med Chem 64: 2714-2724 (2021).
  12. Synthetic nanobody-SARS-CoV-2 receptor-binding domain structures identify distinct epitopes. 7LKW, 7LKX, 7LKS, 7LKR, 7LKU, 7LKT. Ahmad, J., Jiang, J., Boyd, L.F., Natarajan, K., Margulies, D.H. Biorxiv (2021).
  13. Interplay between hevin, SPARC, and MDGAs: modulators of neurexin-neuroligin transsynaptic bridges. 7KBU.  Fan, S., Gangwar, S.P., Machius, M., Rudenko, G. Structure (2021).
  14. Fungal-Selective Resorcylate Aminopyrazole Hsp90 Inhibitors: Optimization of Whole-Cell Anticryptococcal Activity and Insights into the Structural Origins of Cryptococcal Selectivity. 7K9R. Marcyk, P.T., LeBlanc, E.V., Kuntz, D.A., Xue, A., Ortiz, F., Trilles, R., Bengtson, S., Kenney, T.M.G., Huang, D.S., Robbins, N., Williams, N.S., Krysan, D.J., Prive, G.G., Whitesell, L., Cowen, L.E., Brown, L.E. J Med Chem 64: 1139-1169 (2021).
  15. Substituted diaryl ether compounds as retinoic acid-related orphan Receptor-gamma t (ROR gamma t) agonists. 7KXF, 7KXD, 7KXE. Ruan, Z., Park, P.K., Wei, D., Purandare, A., Wan, H., O’Malley, D., Stachura, S., Perez, H., Cavallaro, C.L., Weigelt, C.A., Sack, J.S., Ruzanov, M., Khan, J., Gururajan, M., Wong, J.J., Huang, Y., Yarde, M., Li, Z., Chen, C., Sun, H., Borowski, V., Xie, J.H., Anthony, M., Agler, M., Fink, B.E., Harikrishnan, L.S. Bioorg Med Chem Lett 35: 127778-127778 (2021).
  16. Development of Orally Efficacious Allosteric Inhibitors of TNF alpha via Fragment-Based Drug Design. 6X85, 6X82, 6X83, 6X81. Dietrich, J.D., Longenecker, K.L., Wilson, N.S., Goess, C., Panchal, S.C., Swann, S.L., Petros, A.M., Hobson, A.D., Ihle, D., Song, D., Richardson, P., Comess, K.M., Cox, P.B., Dombrowski, A., Sarris, K., Donnelly-Roberts, D.L., Duignan, D.B., Gomtsyan, A., Jung, P., Krueger, A.C., Mathieu, S., McClure, A., Stoll, V.S., Wetter, J., Mankovich, J.A., Hajduk, P.J., Vasudevan, A., Stoffel, R.H., Sun, C.  J Med Chem 64: 417-429 (2021).
  17. PF-07059013: A Noncovalent Modulator of Hemoglobin for Treatment of Sickle Cell Disease. 7JY3, 7JY1, 7JY0, 7JYZ. Gopalsamy, A., Aulabaugh, A.E., Barakat, A., Beaumont, K.C., Cabral, S., Canterbury, D.P., Casimiro-Garcia, A., Chang, J.S., Chen, M.Z., Choi, C., Dow, R.L., Fadeyi, O.O., Feng, X., France, S.P., Howard, R.M., Janz, J.M., Jasti, J., Jasuja, R., Jones, L.H., King-Ahmad, A., Knee, K.M., Kohrt, J.T., Limberakis, C., Liras, S., Martinez, C.A., McClure, K.F., Narayanan, A., Narula, J., Novak, J.J., O’Connell, T.N., Parikh, M.D., Piotrowski, D.W., Plotnikova, O., Robinson, R.P., Sahasrabudhe, P.V., Sharma, R., Thuma, B.A., Vasa, D., Wei, L., Wenzel, A.Z., Withka, J.M., Xiao, J., Yayla, H.G.  J Med Chem 64: 326-342 (2021).
  18. Using yeast surface display to engineer a soluble and crystallizable construct of hematopoietic progenitor kinase 1 (HPK1). 7KAC. Lau, W.L., Pearce, B., Malakian, H., Rodrigo, I., Xie, D., Gao, M., Marsilio, F., Chang, C., Ruzanov, M., Muckelbauer, J.K., Newitt, J.A., Lipovsek, D., Sheriff, S. Acta Crystallogr F Struct Biol Commun 77: 22-28 (2021).
  19. Development of Orally Efficacious Allosteric Inhibitors of TNF alpha via Fragment-Based Drug Design. 6X86. Dietrich, J.D., Longenecker, K.L., Wilson, N.S., Goess, C., Panchal, S.C., Swann, S.L., Petros, A.M., Hobson, A.D., Ihle, D., Song, D., Richardson, P., Comess, K.M., Cox, P.B., Dombrowski, A., Sarris, K., Donnelly-Roberts, D.L., Duignan, D.B., Gomtsyan, A., Jung, P., Krueger, A.C., Mathieu, S., McClure, A., Stoll, V.S., Wetter, J., Mankovich, J.A., Hajduk, P.J., Vasudevan, A., Stoffel, R.H., Sun, C.  J Med Chem 64: 417-429 (2021).
  20. Structure-Based Drug Design and Synthesis of PI3K alpha-Selective Inhibitor (PF-06843195). 7K6O, 7K6N, 7K6M. Cheng, H., Orr, S.T.M., Bailey, S., Brooun, A., Chen, P., Deal, J.G., Deng, Y.L., Edwards, M.P., Gallego, G.M., Grodsky, N., Huang, B., Jalaie, M., Kaiser, S., Kania, R.S., Kephart, S.E., Lafontaine, J., Ornelas, M.A., Pairish, M., Planken, S., Shen, H., Sutton, S., Zehnder, L., Almaden, C.D., Bagrodia, S., Falk, M.D., Gukasyan, H.J., Ho, C., Kang, X., Kosa, R.E., Liu, L., Spilker, M.E., Timofeevski, S., Visswanathan, R., Wang, Z., Meng, F., Ren, S., Shao, L., Xu, F., Kath, J.C.  J Med Chem 64: 644-661 (2021).
  21. Small Molecule Inhibitors of the Bacterioferritin (BfrB)-Ferredoxin (Bfd) Complex Kill Biofilm-Embedded Pseudomonas aeruginosa Cells. 7K5F, 7K5E, 7K5H, 7K5G. Soldano, A., Yao, H., Punchi Hewage, A.N.D., Meraz, K., Annor-Gyamfi, J.K., Bunce, R.A., Battaile, K.P., Lovell, S., Rivera, M. ACS Infect Dis 7: 123-140 (2021).
  22. Costameric integrin and sarcoglycan protein levels are altered in a Drosophila model for Limb-girdle muscular dystrophy type 2H. 6XG7. Bawa, S., Gameros, S., Baumann, K., Brooks, D.S., Kollhoff, J.A., Zolkiewski, M., Re Cecconi, A.D., Panini, N., Russo, M., Piccirillo, R., Johnson, D.K., Kashipathy, M.M., Battaile, K.P., Lovell, S., Bouyain, S.E.A., Kawakami, J., Geisbrecht, E.R. Mol Biol Cell 32: 260-273 (2021).
  23. Structural insight into the novel iron-coordination and domain interactions of transferrin-1 from a model insect, Manduca sexta. 6WB6. Weber, J.J., Kashipathy, M.M., Battaile, K.P., Go, E., Desaire, H., Kanost, M.R., Lovell, S., Gorman, M.J. Protein Sci 30: 408-422 (2021).
2020

 

  1. Discovery of AZD4573, a Potent and Selective Inhibitor of CDK9 That Enables Short Duration of Target Engagement for the Treatment of Hematological Malignancies. 6Z45. Barlaam, B., Casella, R., Cidado, J., Cook, C., De Savi, C., Dishington, A., Donald, C.S., Drew, L., Ferguson, A.D., Ferguson, D., Glossop, S., Grebe, T., Gu, C., Hande, S., Hawkins, J., Hird, A.W., Holmes, J., Horstick, J., Jiang, Y., Lamb, M.L., McGuire, T.M., Moore, J.E., O’Connell, N., Pike, A., Pike, K.G., Proia, T., Roberts, B., San Martin, M., Sarkar, U., Shao, W., Stead, D., Sumner, N., Thakur, K., Vasbinder, M.M., Varnes, J.G., Wang, J., Wang, L., Wu, D., Wu, L., Yang, B., Yao, T.  J Med Chem 63: 15564-15590 (2020).
  2. Crystal Structure and Characterization of Human Heavy-Chain Only Antibodies Reveals a Novel, Stable Dimeric Structure Similar to Monoclonal Antibodies. 7KQY. Mieczkowski, C., Bahmanjah, S., Yu, Y., Baker, J., Raghunathan, G., Tomazela, D., Hsieh, M., McCoy, M., Strickland, C., Fayadat-Dilman, L. Antibodies (Basel) 9 (2020).
  3. A substrate binding model for the KEOPS tRNA modifying complex. 7KJT. Beenstock, J., Ona, S.M., Porat, J., Orlicky, S., Wan, L.C.K., Ceccarelli, D.F., Maisonneuve, P., Szilard, R.K., Yin, Z., Setiaputra, D., Mao, D.Y.L., Khan, M., Raval, S., Schriemer, D.C., Bayfield, M.A., Durocher, D., Sicheri, F. Nat Commun 11: 6233-6233 (2020).
  4. SAXS studies of X-ray induced disulfide bond damage: Engineering high-resolution insight from a low-resolution technique. 6VE1. Stachowski, T.R., Snell, M.E., Snell, E.H.  PLoS One 15: e0239702-e0239702 (2020).
  5. Novel Tricyclic Pyroglutamide Derivatives as Potent ROR gamma t Inverse Agonists Identified using a Virtual Screening Approach. 7JYM. Liu, Q., Batt, D.G., Weigelt, C.A., Yip, S., Wu, D.R., Ruzanov, M., Sack, J.S., Wang, J., Yarde, M., Li, S., Shuster, D.J., Xie, J.H., Sherry, T., Obermeier, M.T., Fura, A., Stefanski, K., Cornelius, G., Khandelwal, P., Tino, J.A., Macor, J.E., Salter-Cid, L., Denton, R., Zhao, Q., Dhar, T.G.M. ACS Med Chem Lett 11: 2510-2518 (2020).
  6. Discovery of Tyrosine Kinase 2 (TYK2) Inhibitor (PF-06826647) for the Treatment of Autoimmune Diseases. 6X8E, 6X8F. 6X8G. Gerstenberger, B.S., Ambler, C., Arnold, E.P., Banker, M.E., Brown, M.F., Clark, J.D., Dermenci, A., Dowty, M.E., Fensome, A., Fish, S., Hayward, M.M., Hegen, M., Hollingshead, B.D., Knafels, J.D., Lin, D.W., Lin, T.H., Owen, D.R., Saiah, E., Sharma, R., Vajdos, F.F., Xing, L., Yang, X., Yang, X., Wright, S.W. J Med Chem 63: 13561-13577 (2020).
  7. Discovery of Highly Selective and Potent HDAC3 Inhibitors Based on a 2-Substituted Benzamide Zinc Binding Group. 7KBH, 7KKn, 7KKM, 7KKP, 7KKO, 7KKQ, 7KK4, 7KK3, 7KK6, 7KK5, 7KK2. Liu, J., Yu, Y., Kelly, J., Sha, D., Alhassan, A.B., Yu, W., Maletic, M.M., Duffy, J.L., Klein, D.J., Holloway, M.K., Carroll, S., Howell, B.J., Barnard, R.J.O., Wolkenberg, S., Kozlowski, J.A. ACS Med Chem Lett 11: 2476-2483 (2020).
  8. Structural Characterization of BTK:PROTAC:cIAP Ternary Complexes: From Snapshots to Ensembles. 6W7O. Calabrese, M.F., Schiemer, J.S., Horst, R., Meng, Y., Montgomery, J., Xu, Y., Feng, X., Borzilleri, K., Uccello, D.P., Leverett, C., Brown, S., Che, Y., Brown, M.F., Hayward, M.M., Gilbert, A.M., Noe, M.C. Nat Chem Biol. Feb;17(2):152-160 (2021). 
  9. Structure of the Diphtheria Toxin at Acidic pH: Implications for the Conformational Switching of the Translocation Domain. 7K7D, 7K7C, 7K7E, 7K7B. Rodnin, M.V., Kashipathy, M.M., Kyrychenko, A., Battaile, K.P., Lovell, S., Ladokhin, A.S. Toxins (Basel) 12 (2020).
  10. Series of Novel and Highly Potent Cyclic Peptide PCSK9 Inhibitors Derived from an mRNA Display Screen and Optimized via Structure-Based Design. 6XIB, 6XID, 6XIC, 6XIF, 6XIE. Alleyne, C., Amin, R.P., Bhatt, B., Bianchi, E., Blain, J.C., Boyer, N., Branca, D., Embrey, M.W., Ha, S.N., Jette, K., Johns, D.G., Kerekes, A.D., Koeplinger, K.A., LaPlaca, D., Li, N., Murphy, B., Orth, P., Ricardo, A., Salowe, S., Seyb, K., Shahripour, A., Stringer, J.R., Sun, Y., Tracy, R., Wu, C., Xiong, Y., Youm, H., Zokian, H.J., Tucker, T.J. J Med Chem 63: 13796-13824 (2020).
  11. Hit-to-lead optimization and discovery of a potent, and orally bioavailable G protein coupled receptor kinase 2 (GRK2) inhibitor. 7K7L, 7K7Z. Xu, G., Gaul, M.D., Liu, Z., DesJarlais, R.L., Qi, J., Wang, W., Krosky, D., Petrounia, I., Milligan, C.M., Hermans, A., Lu, H.R., Huang, D.Z., Xu, J.Z., Spurlino, J.C. Bioorg Med Chem Lett 30: 127602-127602 (2020).
  12. Discovery of A-1331852, a First-in-Class, Potent, and Orally-Bioavailable BCL-XL Inhibitor. PDB 6VWC. Wang, L., Doherty, G.A., Judd, A.S., Tao, Z., Hansen, T.M., Frey, R.R., Song, X., Kunzer, A.R., Wang, X., Wendt, M.D., Flygare, J.A., Catron, N.D., Judge, R.A., Park, C.H., Shekhar, S., Phillips, D.C., Nimmer, P., Smith, M.L., Tahir, S.K., Xiao, Y., Xue, J., Zhang, H., Le, P.N., Mitten, M.J., Boghaert, E.R., Gao, W., Kovar, P.J., Choo, E.F., Diaz, D., Fairbrother, W.J., Elmore, S.W., Sampath, D., Leverson, J.D., Souers, A.J. ACS Med Chem Lett 11: 1829-1836 (2020).
  13. Structural characterization of the ICOS/ICOS-L immune complex reveals high molecular mimicry by therapeutic antibodies. PDB 6X4G. Rujas, E., Cui, H., Sicard, T., Semesi, A., Julien, J.P. Nat Commun. 11: 5066-5066 (2020).
  14. Discovery and structure activity relationships of 7-benzyl triazolopyridines as stable, selective, and reversible inhibitors of myeloperoxidase. PDB 6WY0, 6WY5, 6WY7, 6WYD, 6WXZ, Shaw, S.A., Vokits, B.P., Dilger, A.K., Viet, A., Clark, C.G., Abell, L.M., Locke, G.A., Duke, G., Kopcho, L.M., Dongre, A., Gao, J., Krishnakumar, A., Jusuf, S., Khan, J., Spronk, S.A., Basso, M.D., Zhao, L., Cantor, G.H., Onorato, J.M., Wexler, R.R., Duclos, F., Kick, E.K. Bioorg Med Chem
  15. Structure-Guided Optimization of Dipeptidyl Inhibitors of Norovirus 3CL Protease. PDB 6W5L, 6W5H, 6W5K, 6W5J. Rathnayake, A.D., Kim, Y., Dampalla, C.S., Nguyen, H.N., Jesri, A.M., Kashipathy, M.M., Lushington, G.H., Battaile, K.P., Lovell, S., Chang, K.O., Groutas, W.C. J Med Chem.
  16. Allosteric regulation of lysosomal enzyme recognition by the cation-independent mannose 6-phosphate receptor. PDB 6V02 Olson, L.J., Misra, S.K., Ishihara, M., Battaile, K.P., Grant, O.C., Sood, A., Woods, R.J., Kim, J.P., Tiemeyer, M., Ren, G., Sharp, J.S., Dahms, N.M. Commun Biol.
  17. Identification of TNO155, an Allosteric SHP2 Inhibitor for the Treatment of Cancer. PDB 7JVM, 7JVN.  LaMarche, M.J., Acker, M.G., Argintaru, A., Bauer, D., Boisclair, J., Chan, H., Chen, C., Chen, Y.P., Chen, Z., Deng, Z., Dore, M., Dunstan, D., Fan, J., Fekkes, P., Firestone, B., Fodor, M., Garcia-Fortanet, J., Fortin, P.D., Fridrich, C., Giraldes, J., Glick, M., Grunenfelder, D., Hao, H.X., Hentemann, M., Ho, S., Jouk, A., Kang, Z.B., Karki, R., Kato, M., Keen, N., Koenig, R., LaBonte, L.R., Larrow, J., Liu, G., Liu, S., Majumdar, D., Mathieu, S., Meyer, M., Mohseni, M., Ntaganda, R., Palermo, M., Perez, L.B., Pu, M., Ramsey, T., Reilly, J., Sarver, P., Sellers, W.R., Sendzick, M., Shultz, M.D., Slisz, J., Slocum, K., Smith, T., Spence, S., Stams, T., Straub, C., Tamez, V., Toure, B.B., Towler, C., Wang, P., Wang, H., Williams, S.L., Yang, F., Yu, B., Zhang, J.H., Zhu, S. J Med Chem.
  18. Discovery and Functional Characterization of hPT3, a Humanized Anti-Phospho Tau Selective Monoclonal Antibody. PDB 6XLI. Van Kolen, K., Malia, T.J., Theunis, C., Nanjunda, R., Teplyakov, A., Ernst, R., Wu, S.J., Luo, J., Borgers, M., Vandermeeren, M., Bottelbergs, A., Wintmolders, C., Lacy, E., Maurin, H., Larsen, P., Willems, R., Van De Casteele, T., Triana-Baltzer, G., Slemmon, R., Galpern, W., Trojanowski, J.Q., Sun, H., Mercken, M.H. J Alzheimers Dis.
  19. Discovery of PF-06835919: A Potent Inhibitor of Ketohexokinase (KHK) for the Treatment of Metabolic Disorders Driven by the Overconsumption of Fructose. PDB 6W0N, 6W0X, 6W0W, 6W0Z, 6W0Y. Futatsugi, K., Smith, A.C., Tu, M., Raymer, B., Ahn, K., Coffey, S.B., Dowling, M.S., Fernando, D.P., Gutierrez, J.A., Huard, K., Jasti, J., Kalgutkar, A.S., Knafels, J.D., Pandit, J., Parris, K.D., Perez, S., Pfefferkorn, J.A., Price, D.A., Ryder, T., Shavnya, A., Stock, I.A., Tsai, A.S., Tesz, G.J., Thuma, B.A., Weng, Y., Wisniewska, H., Xing, G., Zhou, J., Magee, T.V. J Med Chem.
  20. Structure-based amelioration of PXR transactivation in a novel series of macrocyclic allosteric inhibitors of HIV-1 integrase. PDB 6XP9. Sivaprakasam, P., Wang, Z., Meanwell, N.A., Khan, J.A., Langley, D.R., Johnson, S.R., Li, G., Pendri, A., Connolly, T.P., Gao, M., Camac, D.M., Klakouski, C., Zvyaga, T., Cianci, C., McAuliffe, B., Ding, B., Discotto, L., Krystal, M.R., Jenkins, S., Peese, K.M., Narasimhulu Naidu, B.. Bioorg Med Chem Lett.
  21. Tricyclic sulfones as potent, selective and efficacious ROR gamma t inverse agonists – Exploring C6 and C8 SAR using late-stage functionalization. PDB 7JTM. Shi, Q., Xiao, Z., Yang, M.G., Marcoux, D., Cherney, R.J., Yip, S., Li, P., Wu, D.R., Weigelt, C.A., Sack, J., Khan, J., Ruzanov, M., Wang, J., Yarde, M., Ellen Cvijic, M., Li, S., Shuster, D.J., Xie, J., Sherry, T., Obermeier, M., Fura, A., Stefanski, K., Cornelius, G., Chacko, S., Shu, Y.Z., Khandelwal, P., Hynes Jr., J., Tino, J.A., Salter-Cid, L., Denton, R., Zhao, Q., Dhar, T.G.M. Bioorg Med Chem Lett.
  22. BTN3A1 governs antitumor responses by coordinating alpha beta and gamma delta T cells. PDB 6XLQ. Payne, K.K., Mine, J.A., Biswas, S., Chaurio, R.A., Perales-Puchalt, A., Anadon, C.M., Costich, T.L., Harro, C.M., Walrath, J., Ming, Q., Tcyganov, E., Buras, A.L., Rigolizzo, K.E., Mandal, G., Lajoie, J., Ophir, M., Tchou, J., Marchion, D., Luca, V.C., Bobrowicz, P., McLaughlin, B., Eskiocak, U., Schmidt, M., Cubillos-Ruiz, J.R., Rodriguez, P.C., Gabrilovich, D.I., Conejo-Garcia, J.R. Science.
  23. An orally available non-nucleotide STING agonist with antitumor activity.PDB 6UKW, 6UKV, 6UKY, 6UKX, 6UKM. Pan, B.S., Perera, S.A., Piesvaux, J.A., Presland, J.P., Schroeder, G.K., Cumming, J.N., Trotter, B.W., Altman, M.D., Buevich, A.V., Cash, B., Cemerski, S., Chang, W., Chen, Y., Dandliker, P.J., Feng, G., Haidle, A., Henderson, T., Jewell, J., Kariv, I., Knemeyer, I., Kopinja, J., Lacey, B.M., Laskey, J., Lesburg, C.A., Liang, R., Long, B.J., Lu, M., Ma, Y., Minnihan, E.C., O’Donnell, G., Otte, R., Price, L., Rakhilina, L., Sauvagnat, B., Sharma, S., Tyagarajan, S., Woo, H., Wyss, D.F., Xu, S., Bennett, D.J., Addona, G.H. Science.
  24. Discovery of 2,6-difluorobenzyl ether series of phenyl ((R)-3-phenylpyrrolidin-3-yl)sulfones as surprisingly potent, selective and orally bioavailable ROR gamma t inverse agonists. PDB 7JH2. Duan, J.J., Jiang, B., Lu, Z., Stachura, S., Weigelt, C.A., Sack, J.S., Khan, J., Ruzanov, M., Wu, D.R., Yarde, M., Shen, D.R., Zhao, Q., Salter-Cid, L.M., Carter, P.H., Murali Dhar, T.G. Bioorg Med Chem Lett.
  25. Identification of potent inhibitors of the sortilin-progranulin interaction. PDB 6X4H. Stachel, S.J., Ginnetti, A.T., Johnson, S.A., Cramer, P., Wang, Y., Bukhtiyarova, M., Krosky, D., Stump, C., Hurzy, D.M., Schlegel, K.A., Cooke, A.J., Allen, S., O’Donnell, G., Ziebell, M., Parthasarathy, G., Getty, K.L., Ho, T., Ou, Y., Jovanovska, A., Carroll, S.S., Pausch, M., Lumb, K., Mosser, S.D., Voleti, B., Klein, D.J., Soisson, S.M., Zerbinatti, C., Coleman, P.J. Bioorg Med Chem Lett.
  26. Development of a selective HDAC inhibitor aimed at reactivating the HIV latent reservoir. PDB 6XEB, 6XEC. Clausen, D.J., Liu, J., Yu, W., Duffy, J.L., Chung, C.C., Myers, R.W., Klein, D.J., Fells, J., Holloway, K., Wu, J., Wu, G., Howell, B.J., Barnard, R.J.O., Kozlowski, J. Bioorg Med Chem Lett.
  27. Discovery of (3S,4S)-3-methyl-3-(4-fluorophenyl)-4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxyprop-2-yl)phenyl)pyrrolidines as novel ROR gamma t inverse agonists. PDB 6XFV. Jiang, B., Duan, J.J., Stachura, S., Karmakar, A., Hemagiri, H., Raut, D.K., Gupta, A.K., Weigelt, C.A., Khan, J., Sack, J.S., Wu, D.R., Yarde, M., Shen, D.R., Galella, M.A., Mathur, A., Zhao, Q., Salter-Cid, L.M., Carter, P.H., Dhar, T.G.M. Bioorg Med Chem Lett.
  28. 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV-infected mice. PDB 6W2A. Rathnayake, A.D., Zheng, J., Kim, Y., Perera, K.D., Mackin, S., Meyerholz, D.K., Kashipathy, M.M., Battaile, K.P., Lovell, S., Perlman, S., Groutas, W.C., Chang, K.O. Sci Transl Med.
  29. Discovery of Potent and Orally Bioavailable Small Molecule Antagonists of Toll-like Receptors 7/8/9 (TLR7/8/9). PDB 6V9U. Mussari, C.P., Dodd, D.S., Sreekantha, R.K., Pasunoori, L., Wan, H., Posy, S.L., Critton, D., Ruepp, S., Subramanian, M., Watson, A., Davies, P., Schieven, G.L., Salter-Cid, L.M., Srivastava, R., Tagore, D.M., Dudhgaonkar, S., Poss, M.A., Carter, P.H., Dyckman, A.J. ACS Med Chem Lett.
  30. 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV-infected mice. PDB 6VGZ, 6VGY, 6VH1, 6VH0, 6VH3, 6VH2, 6XMK. Rathnayake, A.D., Zheng, J., Kim, Y., Perera, K.D., Mackin, S., Meyerholz, D.K., Kashipathy, M.M., Battaile, K.P., Lovell, S., Perlman, S., Groutas, W.C., Chang, K.O. Sci Transl Med.
  31. Selective Class I HDAC Inhibitors Based on Aryl Ketone Zinc Binding Induce HIV-1 Protein for Clearance. PDB 6XDM. Liu, J., Kelly, J., Yu, W., Clausen, D., Yu, Y., Kim, H., Duffy, J.L., Chung, C.C., Myers, R.W., Carroll, S., Klein, D.J., Fells, J., Holloway, M.K., Wu, J., Wu, G., Howell, B.J., Barnard, R.J.O., Kozlowski, J.A. ACS Med Chem Lett.
  32. Potent, non-covalent reversible BTK inhibitors with 8-amino-imidazo[1,5-a]pyrazine core featuring 3-position bicyclic ring substitutes. PDB 6X3N, 6X3P, 6X3O. Liu, J., Guiadeen, D., Krikorian, A., Gao, X., Wang, J., Babu Boga, S., Alhassan, A.B., Yu, W., Selyutin, O., Yu, Y., Anand, R., Xu, J., Kelly, J., Duffy, J.L., Liu, S., Yang, C., Wu, H., Cai, J., Bennett, C., Maloney, K.M., Tyagarajan, S., Gao, Y.D., Fischmann, T.O., Presland, J., Mansueto, M., Xu, Z., Leccese, E., Zhang-Hoover, J., Knemeyer, I., Garlisi, C.G., Stivers, P., Brandish, P.E., Hicks, A., Kim, R., Kozlowski, J.A. Bioorg Med Chem Lett.
  33. Structure-guided reshaping of the acyl binding pocket of ‘TesA thioesterase enhances octanoic acid production in E. coli. PDB 6LFB. Deng, X., Chen, L., Hei, M., Liu, T., Feng, Y., Yang, G.Y. Metab Eng.
  34. A glycoprotein B-neutralizing antibody structure at 2.8 angstrom uncovers a critical domain for herpesvirus fusion initiation. PDB 6VLK. Oliver, S.L., Xing, Y., Chen, D.H., Roh, S.H., Pintilie, G.D., Bushnell, D.A., Sommer, M.H., Yang, E., Carfi, A., Chiu, W., Arvin, A.M. Nat. Commun.
  35. Structural analysis of the catalytic domain of Artemis endonuclease/SNM1C reveals distinct structural features. PDB 6WO0. Karim, M.F., Liu, S., Laciak, A.R., Volk, L., Koszelak-Rosenblum, M., Lieber, M.R., Wu, M., Curtis, R., Huang, N.N., Carr, G., Zhu, G. J Biol Chem.
  36. Structure-Based Design and Preclinical Characterization of Selective and Orally Bioavailable Factor XIa Inhibitors: Demonstrating the Power of an Integrated S1 Protease Family Approach. PDB 6USY. Lorthiois, E., Roache, J., Barnes-Seeman, D., Altmann, E., Hassiepen, U., Turner, G., Duvadie, R., Hornak, V., Karki, R.G., Schiering, N., Weihofen, W.A., Perruccio, F., Calhoun, A., Fazal, T., Dedic, D., Durand, C., Dussauge, S., Fettis, K., Tritsch, F., Dentel, C., Druet, A., Liu, D., Kirman, L., Lachal, J., Namoto, K., Bevan, D., Mo, R., Monnet, G., Muller, L., Zessis, R., Huang, X., Lindsley, L., Currie, T., Chiu, Y.H., Fridrich, C., Delgado, P., Wang, S., Hollis-Symynkywicz, M., Berghausen, J., Williams, E., Liu, H., Liang, G., Kim, H., Hoffmann, P., Hein, A., Ramage, P., D’Arcy, A., Harlfinger, S., Renatus, M., Ruedisser, S., Feldman, D., Elliott, J., Sedrani, R., Maibaum, J., Adams, C.M. J Med Chem.
  37. Characterization of SpecificN-alpha-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library. PDB 6WF5, 6WF3, 6WFN, 6WFO, 6WFG, 6WFK. Kung, P.P., Bingham, P., Burke, B.J., Chen, Q., Cheng, X., Deng, Y.L., Dou, D., Feng, J., Gallego, G.M., Gehring, M.R., Grant, S.K., Greasley, S., Harris, A.R., Maegley, K.A., Meier, J., Meng, X., Montano, J.L., Morgan, B.A., Naughton, B.S., Palde, P.B., Paul, T.A., Richardson, P., Sakata, S., Shaginian, A., Sonnenburg, W.K., Subramanyam, C., Timofeevski, S., Wan, J., Yan, W., Stewart, A.E. ACS Med Chem Lett.
  38. Discovery of hydroxy pyrimidine Factor IXa inhibitors. PDB 6X5L, 6X5P. Jayne, C.L., Andreani, T., Chan, T.Y., Chelliah, M.V., Clasby, M.C., Dwyer, M., Eagen, K.A., Fried, S., Greenlee, W.J., Guo, Z., Hawes, B., Hruza, A., Ingram, R., Keertikar, K.M., Neelamkavil, S., Reichert, P., Xia, Y., Chackalamannil, S. Bioorg Med Chem Lett.
  39. Optimization of Nicotinamides as Potent and Selective IRAK4 Inhibitors with Efficacy in a Murine Model of Psoriasis. PDB 6VQL. Nair, S., Kumar, S.R., Paidi, V.R., Sistla, R., Kantheti, D., Polimera, S.R., Thangavel, S., Mukherjee, A.J., Das, M., Bhide, R.S., Pitts, W.J., Murugesan, N., Dudhgoankar, S., Nagar, J., Subramani, S., Mazumder, D., Carman, J.A., Holloway, D.A., Li, X., Fereshteh, M.P., Ruepp, S., Palanisamy, K., Mariappan, T.T., Maddi, S., Saxena, A., Elzinga, P., Chimalakonda, A., Ruan, Q., Ghosh, K., Bose, S., Sack, J., Yan, C., Kiefer, S.E., Xie, D., Newitt, J.A., Saravanakumar, S.P., Rampulla, R.A., Barrish, J.C., Carter, P.H., Hynes Jr., J. ACS Med Chem Lett.
  40. Crystal structure of human lysosomal acid lipase and its implications in cholesteryl ester storage disease. PDB 6V7N. Rajamohan, F., Reyes, A.R., Tu, M., Nedoma, N.L., Hoth, L.R., Schwaid, A.G., Kurumbail, R.G., Ward, J., Han, S.  J Lipid Res.
  41. Discovery of a High Affinity, Orally Bioavailable Macrocyclic FXIa Inhibitor with Antithrombotic Activity in Preclinical Species. PDB 6W50. Yang, W., Wang, Y., Lai, A., Clark, C.G., Corte, J.R., Fang, T., Gilligan, P.J., Jeon, Y., Pabbisetty, K.B., Rampulla, R.A., Mathur, A., Kaspady, M., Neithnadka, P.R., Arumugam, A., Raju, S., Rossi, K.A., Myers Jr., J.E., Sheriff, S., Lou, Z., Zheng, J.J., Chacko, S.A., Bozarth, J.M., Wu, Y., Crain, E.J., Wong, P.C., Seiffert, D.A., Luettgen, J.M., Lam, P.Y.S., Wexler, R.R., Ewing, W.R. J Med Chem.
  42. Augmenting Hit Identification by Virtual Screening Techniques in Small Molecule Drug Discovery. PDB 6VLM. Yan, X.C., Sanders, J.M., Gao, Y.D., Tudor, M., Haidle, A.M., Klein, D.J., Converso, A., Lesburg, C.A., Zang, Y., Wood, H.B. J Chem Inf Model.
  43. Optimization and biological evaluation of thiazole-bis-amide inverse agonists of ROR gamma t. PDB 6VSW. Gege, C., Albers, M., Kinzel, O., Kleymann, G., Schluter, T., Steeneck, C., Hoffmann, T., Xue, X., Cummings, M.D., Spurlino, J., Milligan, C., Fourie, A.M., Edwards, J.P., Leonard, K., Coe, K., Scott, B., Pippel, D., Goldberg, S.D. Bioorg Med Chem Lett.
  44. Structure of human DPEP3 in complex with the SC-003 antibody Fab fragment reveals basis for lack of dipeptidase activity. PDB 6VGO, 6VGR. Hayashi, K., Longenecker, K.L., Koenig, P., Prashar, A., Hampl, J., Stoll, V., Vivona, S. J Struct Biol.
  45. Discovery ofN-Ethyl-4-[2-(4-fluoro-2,6-dimethyl-phenoxy)-5-(1-hydroxy-1-methyl-ethyl)phenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (ABBV-744), a BET Bromodomain Inhibitor with Selectivity for the Second Bromodomain. PDB 6VIZ, 6VIY, 6VIX, 6VIW. Sheppard, G.S., Wang, L., Fidanze, S.D., Hasvold, L.A., Liu, D., Pratt, J.K., Park, C.H., Longenecker, K., Qiu, W., Torrent, M., Kovar, P.J., Bui, M., Faivre, E., Huang, X., Lin, X., Wilcox, D., Zhang, L., Shen, Y., Albert, D.H., Magoc, T.J., Rajaraman, G., Kati, W.M., McDaniel, K.F. J Med Chem.
  46. Augmenting Hit Identification by Virtual Screening Techniques in Small Molecule Drug Discovery. PDB 6VLV. Yan, X.C., Sanders, J.M., Gao, Y.D., Tudor, M., Haidle, A.M., Klein, D.J., Converso, A., Lesburg, C.A., Zang, Y., Wood, H.B. J Chem Inf Model.
  47. Discovery and Optimization of Rationally Designed Bicyclic Inhibitors of Human Arginase to Enhance Cancer Immunotherapy. PDB 6V7D, 6V7F, 6V7E. Mitcheltree, M.J., Li, D., Achab, A., Beard, A., Chakravarthy, K., Cheng, M., Cho, H., Eangoor, P., Fan, P., Gathiaka, S., Kim, H.Y., Lesburg, C.A., Lyons, T.W., Martinot, T.A., Miller, J.R., McMinn, S., O’Neil, J., Palani, A., Palte, R.L., Sauri, J., Sloman, D.L., Zhang, H., Cumming, J.N., Fischer, C. ACS Med Chem Lett.
  48. Discovery of ethyl ketone-based HDACs 1, 2, and 3 selective inhibitors for HIV latency reactivation. PDB 6WBZ, 6WBW. Yu, W., Liu, J., Yu, Y., Zhang, V., Clausen, D., Kelly, J., Wolkenberg, S., Beshore, D., Duffy, J.L., Chung, C.C., Myers, R.W., Klein, D.J., Fells, J., Holloway, K., Wu, J., Wu, G., Howell, B.J., Barnard, R.J.O., Kozlowski, J. Bioorg Med Chem Lett.
  49. Substituted benzyloxytricyclic compounds as retinoic acid-related orphan receptor gamma t (ROR gamma t) agonists. PDB 6W9I, 6W9H. Harikrishnan, L.S., Gill, P., Kamau, M.G., Qin, L.Y., Ruan, Z., O’Malley, D., Huynh, T., Stachura, S., Cavallaro, C.L., Lu, Z., J-W Duan, J., Weigelt, C.A., Sack, J.S., Ruzanov, M., Khan, J., Gururajan, M., Wong, J.J., Huang, Y., Yarde, M., Li, Z., Chen, C., Sun, H., Borowski, V., Murtaza, A., Fink, B.E.  Bioorg Med Chem Lett.
  50. Design and optimization of a series of 4-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-2-amines: Dual inhibitors of TYK2 and JAK1. PDB 6VNV, 6VNY, 6VNX, 6VNS. Fensome, A., Ambler, C.M., Arnold, E., Banker, M.E., Clark, J.D., Dowty, M.E., Efremov, I.V., Flick, A., Gerstenberger, B.S., Gifford, R.S., Gopalsamy, A., Hegen, M., Jussif, J., Limburg, D.C., Lin, T.H., Pierce, B.S., Sharma, R., Trujillo, J.I., Vajdos, F.F., Vincent, F., Wan, Z.K., Xing, L., Yang, X., Yang, X. Bioorg Med Chem.
  51. Design and optimization of a series of 4-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-2-amines: Dual inhibitors of TYK2 and JAK1. PDB 6W8L. Fensome, A., Ambler, C.M., Arnold, E., Banker, M.E., Clark, J.D., Dowty, M.E., Efremov, I.V., Flick, A., Gerstenberger, B.S., Gifford, R.S., Gopalsamy, A., Hegen, M., Jussif, J., Limburg, D.C., Lin, T.H., Pierce, B.S., Sharma, R., Trujillo, J.I., Vajdos, F.F., Vincent, F., Wan, Z.K., Xing, L., Yang, X., Yang, X. Bioorg Med Chem.
  52. Phosphorylation of ACTN4 Leads to Podocyte Vulnerability and Proteinuric Glomerulosclerosis. PDB 6OA6. Feng, D., Kumar, M., Muntel, J., Gurley, S.B., Birrane, G., Stillman, I.E., Ding, L., Wang, M., Ahmed, S., Schlondorff, J., Alper, S.L., Ferrante, T., Marquez, S.L., Ng, C.F., Novak, R., Ingber, D.E., Steen, H., Pollak, M.R. J Am Soc Nephrol.
  53. Structural insights into conformational switching in latency-associated peptide between transforming growth factor beta-1 bound and unbound states. PDB 6P7J. Stachowski, T.R., Snell, M.E., Snell, E.H. IUCrJ.
  54. Discovery ofN-(Indazol-3-yl)piperidine-4-carboxylic Acids as ROR gamma t Allosteric Inhibitors for Autoimmune Diseases. PDB 6UCG. Zhang, H., Lapointe, B.T., Anthony, N., Azevedo, R., Cals, J., Correll, C.C., Daniels, M., Deshmukh, S., van Eenenaam, H., Ferguson, H., Hegde, L.G., Karstens, W.J., Maclean, J., Miller, J.R., Moy, L.Y., Simov, V., Nagpal, S., Oubrie, A., Palte, R.L., Parthasarathy, G., Sciammetta, N., van der Stelt, M., Woodhouse, J.D., Trotter, B.W., Barr, K. ACS Med Chem Lett.
  55. Discovery and Optimization of Novel Pyrazolopyrimidines as Potent and Orally Bioavailable Allosteric HIV-1 Integrase Inhibitors. PDB 6UM8. Li, G., Meanwell, N.A., Krystal, M.R., Langley, D.R., Naidu, B.N., Sivaprakasam, P., Lewis, H., Kish, K., Khan, J.A., Ng, A., Trainor, G.L., Cianci, C., Dicker, I.B., Walker, M.A., Lin, Z., Protack, T., Discotto, L., Jenkins, S., Gerritz, S.W., Pendri, A. J Med Chem.
  56. Structural basis of specific inhibition of extracellular activation of pro- or latent myostatin by the monoclonal antibody SRK-015. PDB 6UMX. Dagbay, K.B., Treece, E., Streich Jr., F.C., Jackson, J.W., Faucette, R.R., Nikiforov, A., Lin, S.C., Boston, C.J., Nicholls, S.B., Capili, A.D., Carven, G.J. J Biol Chem.
  57. Distinct surfaces on Cdc5/PLK Polo-box domain orchestrate combinatorial substrate recognition during cell division. PDB 6MF6, 6MF5. Almawi, A.W., Langlois-Lemay, L., Boulton, S., Rodriguez Gonzalez, J., Melacini, G., D’Amours, D., Guarne, A. Sci Rep.
  58. Discovery of BMS-986260, a Potent, Selective, and Orally Bioavailable TGF beta R1 Inhibitor as an Immuno-oncology Agent. PDB 5QU0, 5QTZ. Velaparthi, U., Darne, C.P., Warrier, J., Liu, P., Rahaman, H., Augustine-Rauch, K., Parrish, K., Yang, Z., Swanson, J., Brown, J., Dhar, G., Anandam, A., Holenarsipur, V.K., Palanisamy, K., Wautlet, B.S., Fereshteh, M.P., Lippy, J., Tebben, A.J., Sheriff, S., Ruzanov, M., Yan, C., Gupta, A., Gupta, A.K., Vetrichelvan, M., Mathur, A., Gelman, M., Singh, R., Kinsella, T., Murtaza, A., Fargnoli, J., Vite, G., Borzilleri, R.M. ACS Med Chem Lett.
  59. Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer. PDB 6ONY. Faivre, E.J., McDaniel, K.F., Albert, D.H., Mantena, S.R., Plotnik, J.P., Wilcox, D., Zhang, L., Bui, M.H., Sheppard, G.S., Wang, L., Sehgal, V., Lin, X., Huang, X., Lu, X., Uziel, T., Hessler, P., Lam, L.T., Bellin, R.J., Mehta, G., Fidanze, S., Pratt, J.K., Liu, D., Hasvold, L.A., Sun, C., Panchal, S.C., Nicolette, J.J., Fossey, S.L., Park, C.H., Longenecker, K., Bigelow, L., Torrent, M., Rosenberg, S.H., Kati, W.M., Shen, Y. Nature.
  60. Orally bioavailable amine-linked macrocyclic inhibitors of factor XIa. PDB 5QTY. Fang, T., Corte, J.R., Gilligan, P.J., Jeon, Y., Osuna, H., Rossi, K.A., Myers Jr., J.E., Sheriff, S., Lou, Z., Zheng, J.J., Harper, T.W., Bozarth, J.M., Wu, Y., Luettgen, J.M., Seiffert, D.A., Wexler, R.R., Lam, P.Y.S. Bioorg Med Chem Lett,
  61. A non-canonical monovalent zinc finger stabilizes the integration of Cfp1 into the H3K4 methyltransferase complex COMPASS. PDB 6VHF. Yang, Y., Joshi, M., Takahashi, Y.H., Ning, Z., Qu, Q., Brunzelle, J.S., Skiniotis, G., Figeys, D., Shilatifard, A., Couture, J.F. Nucleic Acids Res.
  62. Self-assembly of the bZIP transcription factor Delta FosB. PDB 6UCL. Yin, Z., Venkannagari, H., Lynch, H., Aglyamova, G., Bhandari, M., Machius, M., Nestler, E.J., Robison, A.J., Rudenko, G. Curr Res Struct Biol.
  63. CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing’s sarcoma. PDB 6M8Q. Ross, N.T., Lohmann, F., Carbonneau, S., Fazal, A., Weihofen, W.A., Gleim, S., Salcius, M., Sigoillot, F., Henault, M., Carl, S.H., Rodriguez-Molina, J.B., Miller, H.R., Brittain, S.M., Murphy, J., Zambrowski, M., Boynton, G., Wang, Y., Chen, A., Molind, G.J., Wilbertz, J.H., Artus-Revel, C.G., Jia, M., Akinjiyan, F.A., Turner, J., Knehr, J., Carbone, W., Schuierer, S., Reece-Hoyes, J.S., Xie, K., Saran, C., Williams, E.T., Roma, G., Spencer, M., Jenkins, J., George, E.L., Thomas, J.R., Michaud, G., Schirle, M., Tallarico, J., Passmore, L.A., Chao, J.A., Beckwith, R.E.J. Nat Chem Biol.
  64. Insights into Structural and Dynamical Changes Experienced by Human RNase 6 upon Ligand Binding. PDB 6MV7, 6MV6. Narayanan, C., Bernard, D.N., Letourneau, M., Gagnon, J., Gagne, D., Bafna, K., Calmettes, C., Couture, J.F., Agarwal, P.K., Doucet, N. Biochemistry 59: 755-765 (2020).
  65. From Screening to Targeted Degradation: Strategies for the Discovery and Optimization of Small Molecule Ligands for PCSK9. PDB 6U38, 6U2P, 6U26, Petrilli, W.L., Adam, G.C., Erdmann, R.S., Abeywickrema, P., Agnani, V., Ai, X., Baysarowich, J., Byrne, N., Caldwell, J.P., Chang, W., DiNunzio, E., Feng, Z., Ford, R., Ha, S., Huang, Y., Hubbard, B., Johnston, J.M., Kavana, M., Lisnock, J.M., Liang, R., Lu, J., Lu, Z., Meng, J., Orth, P., Palyha, O., Parthasarathy, G., Salowe, S.P., Sharma, S., Shipman, J., Soisson, S.M., Strack, A.M., Youm, H., Zhao, K., Zink, D.L., Zokian, H., Addona, G.H., Akinsanya, K., Tata, J.R., Xiong, Y., Imbriglio, J.E. Cell Chem Biol. 27: 32-40.e3 (2020).
  66. Serendipitous discovery of aryl boronic acids as beta-lactamase inhibitors. PDB 6UQS, 6UR3, 6UQU, 6UQT. Yang, S.W., Pan, J., Root, Y., Scapin, G., Xiao, L., Su, J. Bioorg Med Chem Lett. 30: 126795-126795 (2020).
  67. Crystal and solution structures of human oncoprotein Musashi-2 N-terminal RNA recognition motif 1. PDB 6NTY. Lan, L., Xing, M., Kashipathy, M., Douglas, J., Gao, P., Battaile, K., Hanzlik, R., Lovell, S., Xu, L. Proteins 88: 573-583 (2020).
  68. Structural and ligand binding analyses of the periplasmic sensor domain of RsbU in Chlamydia trachomatis support a role in TCA cycle regulation. PDB 6MAB. Soules, K.R., Dmitriev, A., LaBrie, S.D., Dimond, Z.E., May, B.H., Johnson, D.K., Zhang, Y., Battaile, K.P., Lovell, S., Hefty, P.S. Mol Microbiol. 113: 68-88 (2020).
  69. Structural and Biological Basis of Small Molecule Inhibition ofEscherichia coliLpxD Acyltransferase Essential for Lipopolysaccharide Biosynthesis. PDB 6P86, 6P84. Ma, X., Prathapam, R., Wartchow, C., Chie-Leon, B., Ho, C.M., De Vicente, J., Han, W., Li, M., Lu, Y., Ramurthy, S., Shia, S., Steffek, M., Uehara, T. ACS Infect Dis. 6: 1480-1489 (2020).
  70. Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer. PDB 6E6J. Faivre, E.J., McDaniel, K.F., Albert, D.H., Mantena, S.R., Plotnik, J.P., Wilcox, D., Zhang, L., Bui, M.H., Sheppard, G.S., Wang, L., Sehgal, V., Lin, X., Huang, X., Lu, X., Uziel, T., Hessler, P., Lam, L.T., Bellin, R.J., Mehta, G., Fidanze, S., Pratt, J.K., Liu, D., Hasvold, L.A., Sun, C., Panchal, S.C., Nicolette, J.J., Fossey, S.L., Park, C.H., Longenecker, K., Bigelow, L., Torrent, M., Rosenberg, S.H., Kati, W.M., Shen, Y. Nature 578: 306-310 (2020).
  71. Identification of RIPK3 Type II Inhibitors Using High-Throughput Mechanistic Studies in Hit Triage. PDB 6OKO. Hart, A.C., Abell, L., Guo, J., Mertzman, M.E., Padmanabha, R., Macor, J.E., Chaudhry, C., Lu, H., O’Malley, K., Shaw, P.J., Weigelt, C., Pokross, M., Kish, K., Kim, K.S., Cornelius, L., Douglas, A.E., Calambur, D., Zhang, P., Carpenter, B., Pitts, W.J. ACS Med Chem Lett. (2020).
2019
  1. Identification of Imidazo[1,2-b]pyridazine Derivatives as Potent, Selective, and Orally Active Tyk2 JH2 Inhibitors. PDB 6NSL. Liu, C., Lin, J., Moslin, R., Tokarski, J.S., Muckelbauer, J., Chang, C., Tredup, J., Xie, D., Park, H., Li, P., Wu, D.R., Strnad, J., Zupa-Fernandez, A., Cheng, L., Chaudhry, C., Chen, J., Chen, C., Sun, H., Elzinga, P., D’arienzo, C., Gillooly, K., Taylor, T.L., McIntyre, K.W., Salter-Cid, L., Lombardo, L.J., Carter, P.H., Aranibar, N., Burke, J.R., Weinstein, D.S. ACS Med Chem Lett.
  2. Design and characterization of mouse IgG1 and IgG2a bispecific antibodies for use in syngeneic models. PDB 6UQC. Wang, F., Tsai, J.C., Davis, J.H., Chau, B., Dong, J., West, S.M., Hogan, J.M., Wheeler, M.L., Bee, C., Morishige, W., Cayton, T., David-Brown, D., Zhang, C., Kozhich, A., Sproul, T., Dollinger, G., Rajpal, A., Strop, P. MAbs.
  3. A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia. PDB 6PKC. Krivtsov, A.V., Evans, K., Gadrey, J.Y., Eschle, B.K., Hatton, C., Uckelmann, H.J., Ross, K.N., Perner, F., Olsen, S.N., Pritchard, T., McDermott, L., Jones, C.D., Jing, D., Braytee, A., Chacon, D., Earley, E., McKeever, B.M., Claremon, D., Gifford, A.J., Lee, H.J., Teicher, B.A., Pimanda, J.E., Beck, D., Perry, J.A., Smith, M.A., McGeehan, G.M., Lock, R.B., Armstrong, S.A. Cancer Cell.
  4. Scaffold Morphing Identifies 3-Pyridyl Azetidine Ureas as Inhibitors of Nicotinamide Phosphoribosyltransferase (NAMPT). PDB 6PEB. Palacios, D.S., Meredith, E.L., Kawanami, T., Adams, C.M., Chen, X., Darsigny, V., Palermo, M., Baird, D., George, E.L., Guy, C., Hewett, J., Tierney, L., Thigale, S., Wang, L., Weihofen, W.A. ACS Med Chem Lett.
  5. Rationally Designed, Conformationally Constrained Inverse Agonists of ROR gamma t-Identification of a Potent, Selective Series with Biologic-Like in Vivo Efficacy. PDB 6U25. Marcoux, D., Duan, J.J., Shi, Q., Cherney, R.J., Srivastava, A.S., Cornelius, L., Batt, D.G., Liu, Q., Beaudoin-Bertrand, M., Weigelt, C.A., Khandelwal, P., Vishwakrishnan, S., Selvakumar, K., Karmakar, A., Gupta, A.K., Basha, M., Ramlingam, S., Manjunath, N., Vanteru, S., Karmakar, S., Maddala, N., Vetrichelvan, M., Gupta, A., Rampulla, R.A., Mathur, A., Yip, S., Li, P., Wu, D.R., Khan, J., Ruzanov, M., Sack, J.S., Wang, J., Yarde, M., Cvijic, M.E., Li, S., Shuster, D.J., Borowski, V., Xie, J.H., McIntyre, K.W., Obermeier, M.T., Fura, A., Stefanski, K., Cornelius, G., Hynes Jr., J., Tino, J.A., Macor, J.E., Salter-Cid, L., Denton, R., Zhao, Q., Carter, P.H., Dhar, T.G.M. J Med Chem.
  6. Discovery of a Series of 5-Azaquinazolines as Orally Efficacious IRAK4 Inhibitors Targeting MyD88L265PMutant Diffuse Large B Cell Lymphoma. PDB 6RFI, 6RFJ. Degorce, S.L., Anjum, R., Bloecher, A., Carbajo, R.J., Dillman, K.S., Drew, L., Halsall, C.T., Lenz, E.M., Lindsay, N.A., Mayo, M.F., Pink, J.H., Robb, G.R., Rosen, A., Scott, J.S., Xue, Y.  J Med Chem.
  7. VISTA is an acidic pH-selective ligand for PSGL-1. PDB 6MVL. Johnston, R.J., Su, L.J., Pinckney, J., Critton, D., Boyer, E., Krishnakumar, A., Corbett, M., Rankin, A.L., Dibella, R., Campbell, L., Martin, G.H., Lemar, H., Cayton, T., Huang, R.Y., Deng, X., Nayeem, A., Chen, H., Ergel, B., Rizzo, J.M., Yamniuk, A.P., Dutta, S., Ngo, J., Shorts, A.O., Ramakrishnan, R., Kozhich, A., Holloway, J., Fang, H., Wang, Y.K., Yang, Z., Thiam, K., Rakestraw, G., Rajpal, A., Sheppard, P., Quigley, M., Bahjat, K.S., Korman, A.J. Nature.
  8. Discovery of Pyridazinone and Pyrazolo[1,5-a]pyridine Inhibitors of C-Terminal Src Kinase. PDB 6PDJ. O’Malley, D.P., Ahuja, V., Fink, B., Cao, C., Wang, C., Swanson, J., Wee, S., Gavai, A.V., Tokarski, J., Critton, D., Paiva, A.A., Johnson, B.M., Szapiel, N., Xie, D. ACS Med Chem Lett.
  9. Discovery and optimization of covalent Bcl-xL antagonists. PDB 6RNU. Mukherjee, H., Su, N., Belmonte, M.A., Hargreaves, D., Patel, J., Tentarelli, S., Aquila, B., Grimster, N.P. Bioorg Med Chem Lett.
  10. Inhibition of HINT1 Modulates Spinal Nociception and NMDA Evoked Behavior in Mice. PDB 6N3Y. Shah, R.M., Peterson, C., Strom, A., Dillenburg, M., Finzel, B., Kitto, K.F., Fairbanks, C., Wilcox, G., Wagner, C.R. ACS Chem Neurosci.
  11. Discovery of MK-8719, a Potent O-GlcNAcase Inhibitor as a Potential Treatment for Tauopathies. PDB 6PM9. Selnick, H.G., Hess, J.F., Tang, C., Liu, K., Schachter, J.B., Ballard, J.E., Marcus, J., Klein, D.J., Wang, X., Pearson, M., Savage, M.J., Kaul, R., Li, T.S., Vocadlo, D.J., Zhou, Y., Zhu, Y., Mu, C., Wang, Y., Wei, Z., Bai, C., Duffy, J.L., McEachern, E.J. J Med Chem.
  12. CD40/anti-CD40 antibody complexes which illustrate agonist and antagonist structural switches. PDB 6PE8, 6PE9. Argiriadi, M.A., Benatuil, L., Dubrovska, I., Egan, D.A., Gao, L., Greischar, A., Hardman, J., Harlan, J., Iyer, R.B., Judge, R.A., Lake, M., Perron, D.C., Sadhukhan, R., Sielaff, B., Sousa, S., Wang, R., McRae, B.L. BMC Mol Cell Biol.
  13. The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis. PDB 6PD1. Rice, K., Batul, K., Whiteside, J., Kelso, J., Papinski, M., Schmidt, E., Pratasouskaya, A., Wang, D., Sullivan, R., Bartlett, C., Weadge, J.T., Van der Kamp, M.W., Moreno-Hagelsieb, G., Suits, M.D., Horsman, G.P. Nat Commun.
  14. Targeting a Large Active Site: Structure-Based Design of Nanomolar Inhibitors of Trypanosoma brucei Trypanothione Reductase. PDB 6OEY, 6OEX. De Gasparo, R., Halgas, O., Harangozo, D., Kaiser, M., Pai, E.F., Krauth-Siegel, R.L., Diederich, F. Chemistry.
  15. Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165. PDB 6NZP. Wrobleski, S.T., Moslin, R., Lin, S., Zhang, Y., Spergel, S., Kempson, J., Tokarski, J.S., Strnad, J., Zupa-Fernandez, A., Cheng, L., Shuster, D., Gillooly, K., Yang, X., Heimrich, E., McIntyre, K.W., Chaudhry, C., Khan, J., Ruzanov, M., Tredup, J., Mulligan, D., Xie, D., Sun, H., Huang, C., D’Arienzo, C., Aranibar, N., Chiney, M., Chimalakonda, A., Pitts, W.J., Lombardo, L., Carter, P.H., Burke, J.R., Weinstein, D.S. J Med Chem.
  16. Identification ofN-Methyl Nicotinamide andN-Methyl Pyridazine-3-Carboxamide Pseudokinase Domain Ligands as Highly Selective Allosteric Inhibitors of Tyrosine Kinase 2 (TYK2). PDB 6NZE, 6NZF, 6NZH. Moslin, R., Zhang, Y., Wrobleski, S.T., Lin, S., Mertzman, M., Spergel, S., Tokarski, J.S., Strnad, J., Gillooly, K., McIntyre, K.W., Zupa-Fernandez, A., Cheng, L., Sun, H., Chaudhry, C., Huang, C., D’Arienzo, C., Heimrich, E., Yang, X., Muckelbauer, J.K., Chang, C., Tredup, J., Mulligan, D., Xie, D., Aranibar, N., Chiney, M., Burke, J.R., Lombardo, L., Carter, P.H., Weinstein, D.S. J Med Chem.
  17. Crystal structures of the naturally fused CS and cytochrome b5reductase (b5R) domains of Ncb5or reveal an expanded CS fold, extensive CS-b5R interactions and productive binding of the NAD(P)+nicotinamide ring. PDB 6MV2, 6MV1. Benson, D.R., Lovell, S., Mehzabeen, N., Galeva, N., Cooper, A., Gao, P., Battaile, K.P., Zhu, H. Acta Crystallogr D Struct Biol.
  18. ATP-specificity of succinyl-CoA synthetase from Blastocystis hominis. PDB 6NO0, 6NO6, 6NO5. Huang, J., Nguyen, V.H., Hamblin, K.A., Maytum, R., van der Giezen, M., Fraser, M.E.  Acta Crystallogr D Struct Biol.
  19. Structures of Hsp90 alpha and Hsp90 beta bound to a purine-scaffold inhibitor reveal an exploitable residue for drug selectivity. PDB 6OLX. Huck, J.D., Que, N.L.S., Sharma, S., Taldone, T., Chiosis, G., Gewirth, D.T. Proteins.
  20. Discovery of piperazic acid peptide deformylase inhibitors with in vivo activity for respiratory tract and skin infections. PDB 6OW7, 6OW2. Spletstoser, J.T., Dreabit, J., Knox, A.N., Benowitz, A., Campobasso, N., Ward, P., Cui, G., Lewandowski, T., McCloskey, L., Aubart, K.M. Bioorg Med Chem Lett.
  21. Small Molecule IL-36 gamma Antagonist as a Novel Therapeutic Approach for Plaque Psoriasis. PDB 6P9E. Todorovic, V., Su, Z., Putman, C.B., Kakavas, S.J., Salte, K.M., McDonald, H.A., Wetter, J.B., Paulsboe, S.E., Sun, Q., Gerstein, C.E., Medina, L., Sielaff, B., Sadhukhan, R., Stockmann, H., Richardson, P.L., Qiu, W., Argiriadi, M.A., Henry, R.F., Herold, J.M., Shotwell, J.B., McGaraughty, S.P., Honore, P., Gopalakrishnan, S.M., Sun, C.C., Scott, V.E. Sci Rep.
  22. 3-Substituted Quinolines as ROR gamma t Inverse Agonists. PDB 6NAD. Tanis, V.M., Venkatesan, H., Cummings, M.D., Albers, M., Kent Barbay, J., Herman, K., Kummer, D.A., Milligan, C., Nelen, M.I., Nishimura, R., Schlueter, T., Scott, B., Spurlino, J., Wolin, R., Woods, C., Xue, X., Edwards, J.P., Fourie, A.M., Leonard, K. Bioorg Med Chem Lett.
  23. Small Molecule Inhibitors of the BfrB-Bfd Interaction Decrease Pseudomonas aeruginosa Fitness and Potentiate Fluoroquinolone Activity. PDB 6NLM, 6NLL, 6NLN, 6NLG, 6NLF, 6NLI, 6NLK, 6NLJ. Punchi Hewage, A.N.D., Yao, H., Nammalwar, B., Gnanasekaran, K.K., Lovell, S., Bunce, R.A., Eshelman, K., Phaniraj, S.M., Lee, M.M., Peterson, B.R., Battaile, K.P., Reitz, A.B., Rivera, M. J Am Chem Soc.
  24. Structure of lipoprotein lipase in complex with GPIHBP1. PDB 6OAZ, 6OAU, 6OB0.  Arora, R., Nimonkar, A.V., Baird, D., Wang, C., Chiu, C.H., Horton, P.A., Hanrahan, S., Cubbon, R., Weldon, S., Tschantz, W.R., Mueller, S., Brunner, R., Lehr, P., Meier, P., Ottl, J., Voznesensky, A., Pandey, P., Smith, T.M., Stojanovic, A., Flyer, A., Benson, T.E., Romanowski, M.J., Trauger, J.W. Proc Natl Acad Sci U S A.
  25. Structure Overhaul Affords a Potent Purine PI3K delta Inhibitor with Improved Tolerability. PDB 6MUM. Methot, J.L., Zhou, H., Kattar, S.D., McGowan, M.A., Wilson, K., Garcia, Y., Deng, Y., Altman, M., Fradera, X., Lesburg, C., Fischmann, T., Li, C., Alves, S., Shah, S., Fernandez, R., Goldenblatt, P., Hill, A., Shaffer, L., Chen, D., Tong, V., McLeod, R.L., Yu, H., Bass, A., Kemper, R., Gatto, N.T., LaFranco-Scheuch, L., Trotter, B.W., Guzi, T., Katz, J.D. J Med Chem.
  26. Multiple conformational states of the HPK1 kinase domain in complex with sunitinib reveal the structural changes accompanying HPK1 trans-regulation. PDB 6NFY, 6NFZ, 6NG0. Johnson, E., McTigue, M., Gallego, R.A., Johnson, T.W., Timofeevski, S., Maestre, M., Fisher, T.S., Kania, R., Sawasdikosol, S., Burakoff, S., Cronin, C.N. J Biol Chem.
  27. Fragment-Based Discovery of an Apolipoprotein E4 (apoE4) Stabilizer. PDB 6NCN, 6NCO. Petros, A.M., Korepanova, A., Jakob, C.G., Qiu, W., Panchal, S.C., Wang, J., Dietrich, J.D., Brewer, J.T., Pohlki, F., Kling, A., Wilcox, K., Lakics, V., Bahnassawy, L., Reinhardt, P., Partha, S.K., Bodelle, P.M., Lake, M., Charych, E.I., Stoll, V.S., Sun, C., Mohler, E.G. J Med Chem.
  28. NECA derivatives exploit the paralog-specific properties of the site 3 side pocket of Grp94, the endoplasmic reticulum Hsp90. PDB 6CYG, 6CYH. Huck, J.D., Que, N.L.S., Immormino, R.M., Shrestha, L., Taldone, T., Chiosis, G., Gewirth, D.T. J Biol Chem.
  29. Crystal Structure of VapBC-1 from Nontypeable Haemophilus influenzae and the Effect of PIN Domain Mutations on Survival during Infection. PDB 6NKL. Molinaro, A.L., Kashipathy, M.M., Lovell, S., Battaile, K.P., Coussens, N.P., Shen, M., Daines, D.A. J Bacteriol.
  30. Structure-based Discovery of Phenyl (3-Phenylpyrrolidin-3-yl)sulfones as Selective, Orally Active ROR gamma t Inverse Agonists. PDB 6O98. Duan, J.J., Lu, Z., Jiang, B., Stachura, S., Weigelt, C.A., Sack, J.S., Khan, J., Ruzanov, M., Galella, M.A., Wu, D.R., Yarde, M., Shen, D.R., Shuster, D.J., Borowski, V., Xie, J.H., Zhang, L., Vanteru, S., Gupta, A.K., Mathur, A., Zhao, Q., Foster, W., Salter-Cid, L.M., Carter, P.H., Dhar, T.G.M.  ACS Med Chem Lett.
  31. 6-Amino-3-methylpyrimidinones as Potent, Selective, and Orally Efficacious SHP2 Inhibitors. PDB 6MDB. Sarver, P., Acker, M., Bagdanoff, J.T., Chen, Z., Chen, Y.N., Chan, H., Firestone, B., Fodor, M., Fortanet, J., Hao, H., Hentemann, M., Kato, M., Koenig, R., LaBonte, L.R., Liu, G., Liu, S., Liu, C., McNeill, E., Mohseni, M., Sendzik, M., Stams, T., Spence, S., Tamez, V., Tichkule, R., Towler, C., Wang, H., Wang, P., Williams, S.L., Yu, B., LaMarche, M.J. J Med Chem.
  32. Optimization of Fused Bicyclic Allosteric SHP2 Inhibitors. PDB 6MDB, 6MDA, 6MDD, 6MDC. Bagdanoff, J.T., Chen, Z., Acker, M., Chen, Y.N., Chan, H., Dore, M., Firestone, B., Fodor, M., Fortanet, J., Hentemann, M., Kato, M., Koenig, R., LaBonte, L.R., Liu, S., Mohseni, M., Ntaganda, R., Sarver, P., Smith, T., Sendzik, M., Stams, T., Spence, S., Towler, C., Wang, H., Wang, P., Williams, S.L., LaMarche, M.J.  J Med Chem.
  33. Molecular Basis of Broad SpectrumN-Glycan Specificity and Processing of Therapeutic IgG Monoclonal Antibodies by Endoglycosidase S2. PDB 6MDV. Klontz, E.H., Trastoy, B., Deredge, D., Fields, J.K., Li, C., Orwenyo, J., Marina, A., Beadenkopf, R., Gunther, S., Flores, J., Wintrode, P.L., Wang, L.X., Guerin, M.E., Sundberg, E.J. ACS Cent Sci.
  34. Aminopyrazole Carboxamide Bruton’s Tyrosine Kinase Inhibitors. Irreversible to Reversible Covalent Reactive Group Tuning. PDB 6MNY. Schnute, M.E., Benoit, S.E., Buchler, I.P., Caspers, N., Grapperhaus, M.L., Han, S., Hotchandani, R., Huang, N., Hughes, R.O., Juba, B.M., Kim, K.H., Liu, E., McCarthy, E., Messing, D., Miyashiro, J.S., Mohan, S., O’Connell, T.N., Ohren, J.F., Parikh, M.D., Schmidt, M., Selness, S.R., Springer, J.R., Thanabal, V., Trujillo, J.I., Walker, D.P., Wan, Z.K., Withka, J.M., Wittwer, A.J., Wood, N.L., Xing, L., Zapf, C.W., Douhan III, J. ACS Med Chem Lett.
  35. Structural Basis of Nav1.7 Inhibition by a Gating-Modifier Spider Toxin. PDB 6N4I. Xu, H., Li, T., Rohou, A., Arthur, C.P., Tzakoniati, F., Wong, E., Estevez, A., Kugel, C., Franke, Y., Chen, J., Ciferri, C., Hackos, D.H., Koth, C.M., Payandeh, J. Cell.
  36. 5,6,7,8-Tetrahydro-1,6-naphthyridine Derivatives as Potent HIV-1-Integrase-Allosteric-Site Inhibitors. PDB 6NCJ. Peese, K.M., Allard, C.W., Connolly, T., Johnson, B.L., Li, C., Patel, M., Sorensen, M.E., Walker, M.A., Meanwell, N.A., McAuliffe, B., Minassian, B., Krystal, M., Parker, D.D., Lewis, H.A., Kish, K., Zhang, P., Nolte, R.T., Simmermacher, J., Jenkins, S., Cianci, C., Naidu, B.N. J Med Chem.
  37. Novel, potent, selective, and brain penetrant phosphodiesterase 10A inhibitors. PDB 6MSA, 6MSC. Geneste, H., Drescher, K., Jakob, C., Laplanche, L., Ochse, M., Torrent, M. Bioorg Med Chem Lett.
  38. Discovery of a Novel cGAMP Competitive Ligand of the Inactive Form of STING. PDB 6MX3, 6MX0, 6MXE. Siu, T., Altman, M.D., Baltus, G.A., Childers, M., Ellis, J.M., Gunaydin, H., Hatch, H., Ho, T., Jewell, J., Lacey, B.M., Lesburg, C.A., Pan, B.S., Sauvagnat, B., Schroeder, G.K., Xu, S. ACS Med Chem Lett.
  39. Putative structural rearrangements associated with the interaction of macrocyclic inhibitors with norovirus 3CL protease. PDB 6BIB, 6BID, 6BIC. Galasiti Kankanamalage, A.C., Weerawarna, P.M., Rathnayake, A.D., Kim, Y., Mehzabeen, N., Battaile, K.P., Lovell, S., Chang, K.O., Groutas, W.C. Proteins.
  40. Discovery of Allosteric, Potent, Subtype Selective, and Peripherally Restricted TrkA Kinase Inhibitors. PDB 6D1Y. Bagal, S.K., Omoto, K., Blakemore, D.C., Bungay, P.J., Bilsland, J.G., Clarke, P.J., Corbett, M.S., Cronin, C.N., Cui, J.J., Dias, R., Flanagan, N.J., Greasley, S.E., Grimley, R., Johnson, E., Fengas, D., Kitching, L., Kraus, M.L., McAlpine, I., Nagata, A., Waldron, G.J., Warmus, J.S. J Med Chem.
2018

 

  1. Reviving B-Factors: Activating ALK Mutations Increase Protein Dynamics of the Unphosphorylated Kinase. PDB 6CDT. Johnson, T.W., Bolanos, B., Brooun, A., Gallego, R.A., Gehlhaar, D., Jalaie, M., McTigue, M., Timofeevski, S. Reviving B-Factors: Activating ALK Mutations Increase Protein Dynamics of the Unphosphorylated Kinase. ACS Med Chem Lett.
  2. Potent Triazolopyridine Myeloperoxidase Inhibitors. PDB 5QJ3, 5QJ2. Wurtz, N.R., Viet, A., Shaw, S.A., Dilger, A., Valente, M.N., Khan, J.A., Jusuf, S., Narayanan, R., Fernando, G., Lo, F., Liu, X., Locke, G.A., Kopcho, L., Abell, L.M., Sleph, P., Basso, M., Zhao, L., Wexler, R.R., Duclos, F., Kick, E.K. ACS Med Chem Lett.
  3. Identification of Cyanamide-Based Janus Kinase 3 (JAK3) Covalent Inhibitors. PDB 6DB3, 6DB4, 6DUD. Casimiro-Garcia, A., Trujillo, J.I., Vajdos, F., Juba, B., Banker, M.E., Aulabaugh, A., Balbo, P., Bauman, J., Chrencik, J., Coe, J.W., Czerwinski, R., Dowty, M., Knafels, J.D., Kwon, S., Leung, L., Liang, S., Robinson, R.P., Telliez, J.B., Unwalla, R., Yang, X., Thorarensen, A. J Med Chem.
  4. Structure-Property Basis for Solving Transporter-Mediated Efflux and Pan-Genotypic Inhibition in HCV NS5B Inhibitors. PDB 5QJ1. Yeung, K.S., Beno, B.R., Mosure, K., Zhu, J., Grant-Young, K.A., Parcella, K., Anjanappa, P., Bora, R.O., Selvakumar, K., Wang, Y.K., Fang, H., Krause, R., Rigat, K., Liu, M., Lemm, J., Sheriff, S., Witmer, M., Tredup, J., Jardel, A., Kish, K., Parker, D., Haskell, R., Santone, K., Meanwell, N.A., Soars, M.G., Roberts, S.B., Kadow, J.F. ACS Med Chem Lett.
  5. Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin. PDB 6CNV, 6CNW. Laursen, N.S., Friesen, R.H.E., Zhu, X., Jongeneelen, M., Blokland, S., Vermond, J., van Eijgen, A., Tang, C., van Diepen, H., Obmolova, G., van der Neut Kolfschoten, M., Zuijdgeest, D., Straetemans, R., Hoffman, R.M.B., Nieusma, T., Pallesen, J., Turner, H.L., Bernard, S.M., Ward, A.B., Luo, J., Poon, L.L.M., Tretiakova, A.P., Wilson, J.M., Limberis, M.P., Vogels, R., Brandenburg, B., Kolkman, J.A., Wilson, I.A. Science.
  6. Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition. PDB 6CRF, 6CRG. LaRochelle, J.R., Fodor, M., Vemulapalli, V., Mohseni, M., Wang, P., Stams, T., LaMarche, M.J., Chopra, R., Acker, M.G., Blacklow, S.C. Nat Commun.
  7. Discovery of Orally Active Inhibitors of Brahma Homolog (BRM)/SMARCA2 ATPase Activity for the Treatment of Brahma Related Gene 1 (BRG1)/SMARCA4-Mutant Cancers. PDB 6EG3, 6EG2. Papillon, J.P.N., Nakajima, K., Adair, C.D., Hempel, J., Jouk, A.O., Karki, R.G., Mathieu, S., Mobitz, H., Ntaganda, R., Smith, T., Visser, M., Hill, S.E., Hurtado, F.K., Chenail, G., Bhang, H.C., Bric, A., Xiang, K., Bushold, G., Gilbert, T., Vattay, A., Dooley, J., Costa, E.A., Park, I., Li, A., Farley, D., Lounkine, E., Yue, Q.K., Xie, X., Zhu, X., Kulathila, R., King, D., Hu, T., Vulic, K., Cantwell, J., Luu, C., Jagani, Z. J Med Chem.
  8. Discovery of 4-Azaindole Inhibitors of TGF beta RI as Immuno-oncology Agents. PDB 5QIL, 5QIK, 5QIN, 5QIM. Zhang, Y., Zhao, Y., Tebben, A.J., Sheriff, S., Ruzanov, M., Fereshteh, M.P., Fan, Y., Lippy, J., Swanson, J., Ho, C.P., Wautlet, B.S., Rose, A., Parrish, K., Yang, Z., Donnell, A.F., Zhang, L., Fink, B.E., Vite, G.D., Augustine-Rauch, K., Fargnoli, J., Borzilleri, R.M. ACS Med Chem Lett.
  9. Development of a Novel B-Cell Lymphoma 6 (BCL6) PROTAC To Provide Insight into Small Molecule Targeting of BCL6. PDB 6EW8, 6EW7, 6EW6. McCoull, W., Cheung, T., Anderson, E., Barton, P., Burgess, J., Byth, K., Cao, Q., Castaldi, M.P., Chen, H., Chiarparin, E., Carbajo, R.J., Code, E., Cowan, S., Davey, P.R., Ferguson, A.D., Fillery, S., Fuller, N.O., Gao, N., Hargreaves, D., Howard, M.R., Hu, J., Kawatkar, A., Kemmitt, P.D., Leo, E., Molina, D.M., O’Connell, N., Petteruti, P., Rasmusson, T., Raubo, P., Rawlins, P.B., Ricchiuto, P., Robb, G.R., Schenone, M., Waring, M.J., Zinda, M., Fawell, S., Wilson, D.M. ACS Chem Biol.
  10. Molecular characterization of the interaction of sialic acid with the periplasmic binding protein from Haemophilus ducreyi. PDB 5Z99, 5ZA4. Gangi Setty, T., Mowers, J.C., Hobbs, A.G., Maiya, S.P., Syed, S., Munson Jr., R.S., Apicella, M.A., Subramanian, R. J. Biol Chem.
  11. Active site residue identity regulates cleavage preference of LAGLIDADG homing endonucleases. PDB 6BCT, 6BCG, 6BCI, 6BCN, 6BCF, 6BCE. McMurrough, T.A., Brown, C.M., Zhang, K., Hausner, G., Junop, M.S., Gloor, G.B., Edgell, D.R. Nucleic Acids Res.
  12. Structure-Guided Design and Procognitive Assessment of a Potent and Selective Phosphodiesterase 2A Inhibitor. PDB 6CYD, 6CYC, 6CYB. Stachel, S.J., Berger, R., Nomland, A.B., Ginnetti, A.T., Paone, D.V., Wang, D., Puri, V., Lange, H., Drott, J., Lu, J., Marcus, J., Dwyer, M.P., Suon, S., Uslaner, J.M., Smith, S.M. ACS Med Chem Lett.
  13. Bfd, a New Class of [2Fe-2S] Protein That Functions in Bacterial Iron Homeostasis, Requires a Structural Anion Binding Site. PDB 6E6R, 6E6Q, 6E6S. Wijerathne, H., Yao, H., Wang, Y., Lovell, S., Battaile, K.P., Rivera, M. Biochemistry.
  14. A Novel Polar Core and Weakly Fixed C-Tail in Squid Arrestin Provide New Insight into Interaction with Rhodopsin. PDB 6BK9. Bandyopadhyay, A., Van Eps, N., Eger, B.T., Rauscher, S., Yedidi, R.S., Moroni, T., West, G.M., Robinson, K.A., Griffin, P.R., Mitchell, J., Ernst, O.P. J Mol Biol.
  15. Structural Determinants of the Stereoinverting Activity of Pseudomonas stutzeri d-Phenylglycine Aminotransferase. PDB 6DVS. Walton, C.J.W., Thiebaut, F., Brunzelle, J.S., Couture, J.F., Chica, R.A. Biochemistry.
  16. Discovery of 3-Cyano- N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1 H-pyrrolo[2,3- b]pyridin-5-yl)benzamide: A Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonist. PDB 6CN6, 6CN5. Schnute, M.E., Wennerstal, M., Alley, J., Bengtsson, M., Blinn, J.R., Bolten, C.W., Braden, T., Bonn, T., Carlsson, B., Caspers, N., Chen, M., Choi, C., Collis, L.P., Crouse, K., Farnegardh, M., Fennell, K.F., Fish, S., Flick, A.C., Goos-Nilsson, A., Gullberg, H., Harris, P.K., Heasley, S.E., Hegen, M., Hromockyj, A.E., Hu, X., Husman, B., Janosik, T., Jones, P., Kaila, N., Kallin, E., Kauppi, B., Kiefer, J.R., Knafels, J., Koehler, K., Kruger, L., Kurumbail, R.G., Kyne Jr., R.E., Li, W., Lofstedt, J., Long, S.A., Menard, C.A., Mente, S., Messing, D., Meyers, M.J., Napierata, L., Noteberg, D., Nuhant, P., Pelc, M.J., Prinsen, M.J., Rhonnstad, P., Backstrom-Rydin, E., Sandberg, J., Sandstrom, M., Shah, F., Sjoberg, M., Sundell, A., Taylor, A.P., Thorarensen, A., Trujillo, J.I., Trzupek, J.D., Unwalla, R., Vajdos, F.F., Weinberg, R.A., Wood, D.C., Xing, L., Zamaratski, E., Zapf, C.W., Zhao, Y., Wilhelmsson, A., Berstein, G. J Med Chem.
  17. Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). PDB 6DBM, 6DBN, 6DBK. Fensome, A., Ambler, C.M., Arnold, E., Banker, M.E., Brown, M.F., Chrencik, J., Clark, J.D., Dowty, M.E., Efremov, I.V., Flick, A., Gerstenberger, B.S., Gopalsamy, A., Hayward, M.M., Hegen, M., Hollingshead, B.D., Jussif, J., Knafels, J.D., Limburg, D.C., Lin, D., Lin, T.H., Pierce, B.S., Saiah, E., Sharma, R., Symanowicz, P.T., Telliez, J.B., Trujillo, J.I., Vajdos, F.F., Vincent, F., Wan, Z.K., Xing, L., Yang, X., Yang, X., Zhang, L. J Med Chem.
  18. Structural Analysis of the Ash2L/Dpy-30 Complex Reveals a Heterogeneity in H3K4 Methylation. PDB 6E2H. Haddad, J.F., Yang, Y., Takahashi, Y.H., Joshi, M., Chaudhary, N., Woodfin, A.R., Benyoucef, A., Yeung, S., Brunzelle, J.S., Skiniotis, G., Brand, M., Shilatifard, A., Couture, J.F. Structure.
  19. Acyl Glucuronide Metabolites of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1 H-indole-3-carboxylic Acid (PF-06409577) and Related Indole-3-carboxylic Acid Derivatives are Direct Activators of Adenosine Monophosphate-Activated Protein Kinase (AMPKK). PDB 6E4U, 6E4W, 6E4T. Ryder, T.F., Calabrese, M.F., Walker, G.S., Cameron, K.O., Reyes, A.R., Borzilleri, K.A., Delmore, J., Miller, R., Kurumbail, R.G., Ward, J., Kung, D.W., Brown, J.A., Edmonds, D.J., Eng, H., Wolford, A.C., Kalgutkar, A.S. J Med Chem.
  20. Structure and Conformational Dynamics of a COMPASS Histone H3K4 Methyltransferase Complex. PDB 6E29. Qu, Q., Takahashi, Y.H., Yang, Y., Hu, H., Zhang, Y., Brunzelle, J.S., Couture, J.F., Shilatifard, A., Skiniotis, G. Cell.
  21. Novel Modes of Inhibition of Wild-Type Isocitrate Dehydrogenase 1 (IDH1): Direct Covalent Modification of His315. PDB 6BKX, 6BKZ, 6BKY, 6BL1, 6BL0, 6BL2. Jakob, C.G., Upadhyay, A.K., Donner, P.L., Nicholl, E., Addo, S.N., Qiu, W., Ling, C., Gopalakrishnan, S.M., Torrent, M., Cepa, S.P., Shanley, J., Shoemaker, A.R., Sun, C.C., Vasudevan, A., Woller, K.R., Shotwell, J.B., Shaw, B., Bian, Z., Hutti, J.E. J Med Chem.
  22. Conservation of Structure and Immune Antagonist Functions of Filoviral VP35 Homologs Present in Microbat Genomes. PDB 6DKU. Edwards, M.R., Liu, H., Shabman, R.S., Ginell, G.M., Luthra, P., Ramanan, P., Keefe, L.J., Kollner, B., Amarasinghe, G.K., Taylor, D.J., Leung, D.W., Basler, C.F. Cell Rep.
  23. Glycan recognition in globally dominant human rotaviruses. PDB 5VX9. Hu, L., Sankaran, B., Laucirica, D.R., Patil, K., Salmen, W., Ferreon, A.C.M., Tsoi, P.S., Lasanajak, Y., Smith, D.F., Ramani, S., Atmar, R.L., Estes, M.K., Ferreon, J.C., Prasad, B.V.V. Nat Commun.
  24. Discovery of Potent, Selective, and Peripherally Restricted Pan-Trk Kinase Inhibitors for the Treatment of Pain. PDB 6DKG, 6DKI.        Bagal, S.K., Andrews, M., Bechle, B.M., Bian, J., Bilsland, J., Blakemore, D.C., Braganza, J.F., Bungay, P.J., Corbett, M.S., Cronin, C.N., Cui, J.J., Dias, R., Flanagan, N.J., Greasley, S.E., Grimley, R., James, K., Johnson, E., Kitching, L., Kraus, M.L., McAlpine, I., Nagata, A., Ninkovic, S., Omoto, K., Scales, S., Skerratt, S.E., Sun, J., Tran-Dube, M., Waldron, G.J., Wang, F., Warmus, J.S. J Med Chem.
  25. X-ray and cryo-EM structures of the mitochondrial calcium uniporter. PDB 6C5R. Fan, C., Fan, M., Orlando, B.J., Fastman, N.M., Zhang, J., Xu, Y., Chambers, M.G., Xu, X., Perry, K., Liao, M., Feng, L. Nature.
  26. Small molecule inhibitors reveal PTK6 kinase is not an oncogenic driver in breast cancers. PDB 6CZ4. Qiu, L., Levine, K., Gajiwala, K.S., Cronin, C.N., Nagata, A., Johnson, E., Kraus, M., Tatlock, J., Kania, R., Foley, T., Sun, S. PLoS One.
  27. Crystal structure of Campylobacter jejuni peroxide regulator. PDB 6DK4. Sarvan, S., Charih, F., Butcher, J., Brunzelle, J.S., Stintzi, A., Couture, J.F. FEBS Lett.
  28. Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36. PDB 5VHE. Chen, M.C., Tippana, R., Demeshkina, N.A., Murat, P., Balasubramanian, S., Myong, S., Ferre-D’Amare, A.R. Nature.
  29. Optimization of permeability in a series of pyrrolotriazine inhibitors of IRAK4. PDB 6F3D, 6F3E, 6F3G, 6F3I. Degorce, S.L., Anjum, R., Dillman, K.S., Drew, L., Groombridge, S.D., Halsall, C.T., Lenz, E.M., Lindsay, N.A., Mayo, M.F., Pink, J.H., Robb, G.R., Scott, J.S., Stokes, S., Xue, Y. Bioorg Med Chem.
  30. Functional insights into the interplay between DNA interaction and metal coordination in ferric uptake regulators. PDB 6D57. Sarvan, S., Charih, F., Askoura, M., Butcher, J., Brunzelle, J.S., Stintzi, A., Couture, J.F. Sci Rep.
  31. Structure of an EIIC sugar transporter trapped in an inward-facing conformation. PDB 6BVG. Ren, Z., Lee, J., Moosa, M.M., Nian, Y., Hu, L., Xu, Z., McCoy, J.G., Ferreon, A.C.M., Im, W., Zhou, M. Proc Natl Acad Sci U S A.
  32. The reactivity-driven biochemical mechanism of covalent KRASG12Cinhibitors. PDB 6B0Y. Hansen, R., Peters, U., Babbar, A., Chen, Y., Feng, J., Janes, M.R., Li, L.S., Ren, P., Liu, Y., Zarrinkar, P.P. Nat Struct Mol Biol.
  33. Using disruptive insertional mutagenesis to identify the in situ structure-function landscape of the Shigella translocator protein IpaB. PDB 5WKQ. Barta, M.L., Tachiyama, S., Muthuramalingam, M., Arizmendi, O., Villanueva, C.E., Ramyar, K.X., Geisbrecht, B.V., Lovell, S., Battaile, K.P., Picking, W.L., Picking, W.D. Protein Sci.
  34. Identification and biological evaluation of thiazole-based inverse agonists of ROR gamma t. PDB 6CVH. Gege, C., Cummings, M.D., Albers, M., Kinzel, O., Kleymann, G., Schluter, T., Steeneck, C., Nelen, M.I., Milligan, C., Spurlino, J., Xue, X., Leonard, K., Edwards, J.P., Fourie, A., Goldberg, S.D., Hoffmann, T. Bioorg Med Chem Lett.
  35. Structure Based Design of a Grp94-Selective Inhibitor: Exploiting a Key Residue in Grp94 To Optimize Paralog-Selective Binding. PDB 6C91. Que, N.L.S., Crowley, V.M., Duerfeldt, A.S., Zhao, J., Kent, C.N., Blagg, B.S.J., Gewirth, D.T. J Med Chem.
  36. A selective peptide inhibitor of Frizzled 7 receptors disrupts intestinal stem cells. PDB 5WBS. Nile, A.H., de Sousa E Melo, F., Mukund, S., Piskol, R., Hansen, S., Zhou, L., Zhang, Y., Fu, Y., Gogol, E.B., Komuves, L.G., Modrusan, Z., Angers, S., Franke, Y., Koth, C., Fairbrother, W.J., Wang, W., de Sauvage, F.J., Hannoush, R.N. Nat Chem Biol.
  37. An orally available, brain-penetrant CAMKK2 inhibitor reduces food intake in rodent model. PDB 6CMJ. Price, D.J., Drewry, D.H., Schaller, L.T., Thompson, B.D., Reid, P.R., Maloney, P.R., Liang, X., Banker, P., Buckholz, R.G., Selley, P.K., McDonald, O.B., Smith, J.L., Shearer, T.W., Cox, R.F., Williams, S.P., Reid, R.A., Tacconi, S., Faggioni, F., Piubelli, C., Sartori, I., Tessari, M., Wang, T.Y. Bioorg Med Chem Lett.
  38. Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer. PDB 6B0F. Tria, G.S., Abrams, T., Baird, J., Burks, H.E., Firestone, B., Gaither, L.A., Hamann, L.G., He, G., Kirby, C.A., Kim, S., Lombardo, F., Macchi, K.J., McDonnell, D.P., Mishina, Y., Norris, J.D., Nunez, J., Springer, C., Sun, Y., Thomsen, N.M., Wang, C., Wang, J., Yu, B., Tiong-Yip, C.L., Peukert, S. J Med Chem.
  39. Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element. PDB 5WKJ, 5WKL, 5WKK, 5WKM. Galasiti Kankanamalage, A.C., Kim, Y., Damalanka, V.C., Rathnayake, A.D., Fehr, A.R., Mehzabeen, N., Battaile, K.P., Lovell, S., Lushington, G.H., Perlman, S., Chang, K.O., Groutas, W.C. Eur J Med Chem.
  40. Crystal structure of B-cell co-receptor CD19 in complex with antibody B43 reveals an unexpected fold. PDB 6AL5. Teplyakov, A., Obmolova, G., Luo, J., Gilliland, G.L. Proteins.
  41. Targeting lysine specific demethylase 4A (KDM4A) tandem TUDOR domain – A fragment based approach. PDB 5VAR. Upadhyay, A.K., Judge, R.A., Li, L., Pithawalla, R., Simanis, J., Bodelle, P.M., Marin, V.L., Henry, R.F., Petros, A.M., Sun, C. Bioorg Med Chem Lett.
  42. Immune-modulating enzyme indoleamine 2,3-dioxygenase is effectively inhibited by targeting its apo-form. PDB 6AZV, 6AZU. Nelp, M.T., Kates, P.A., Hunt, J.T., Newitt, J.A., Balog, A., Maley, D., Zhu, X., Abell, L., Allentoff, A., Borzilleri, R., Lewis, H.A., Lin, Z., Seitz, S.P., Yan, C., Groves, J.T. Proc Natl Acad Sci U S A.
  43. Potent Inhibitors of Hepatitis C Virus NS3 Protease: Employment of a Difluoromethyl Group as a Hydrogen-Bond Donor. PDB 6BQK. Zheng, B., D’Andrea, S.V., Sun, L.Q., Wang, A.X., Chen, Y., Hrnciar, P., Friborg, J., Falk, P., Hernandez, D., Yu, F., Sheaffer, A.K., Knipe, J.O., Mosure, K., Rajamani, R., Good, A.C., Kish, K., Tredup, J., Klei, H.E., Paruchuri, M., Ng, A., Gao, Q., Rampulla, R.A., Mathur, A., Meanwell, N.A., McPhee, F., Scola, P.M. ACS Med Chem Lett.
  44. An Intracellular Allosteric Modulator Binding Pocket in SK2 Ion Channels Is Shared by Multiple Chemotypes. PDB 5V02, 5V03. Cho, L.T., Alexandrou, A.J., Torella, R., Knafels, J., Hobbs, J., Taylor, T., Loucif, A., Konopacka, A., Bell, S., Stevens, E.B., Pandit, J., Horst, R., Withka, J.M., Pryde, D.C., Liu, S., Young, G.T. Structure.
  45. Discovery of Selective RNA-Binding Small Molecules by Affinity-Selection Mass Spectrometry. PDB 6BFB. Rizvi, N.F., Howe, J.A., Nahvi, A., Klein, D.J., Fischmann, T.O., Kim, H.Y., McCoy, M.A., Walker, S.S., Hruza, A., Richards, M.P., Chamberlin, C., Saradjian, P., Butko, M.T., Mercado, G., Burchard, J., Strickland, C., Dandliker, P.J., Smith, G.F., Nickbarg, E.B. ACS Chem Biol.
  46. Heterobicyclic inhibitors of transforming growth factor beta receptor I (TGF beta RI). PDB 6B8Y. Harikrishnan, L.S., Warrier, J., Tebben, A.J., Tonukunuru, G., Madduri, S.R., Baligar, V., Mannoori, R., Seshadri, B., Rahaman, H., Arunachalam, P.N., Dikundwar, A.G., Fink, B.E., Fargnoli, J., Fereshteh, M., Fan, Y., Lippy, J., Ho, C.P., Wautlet, B., Sheriff, S., Ruzanov, M., Borzilleri, R.M. Bioorg Med Chem.
  47. Design of Aminobenzothiazole Inhibitors of Rho Kinases 1 and 2 by Using Protein Kinase A as a Structure Surrogate. PDB 5VHB, 5VI9. Judge, R.A., Vasudevan, A., Scott, V.E., Simler, G.H., Pratt, S.D., Namovic, M.T., Putman, C.B., Aguirre, A., Stoll, V.S., Mamo, M., Swann, S.I., Cassar, S.C., Faltynek, C.R., Kage, K.L., Boyce-Rustay, J.M., Hobson, A.D. Chembiochem.
  48. Identification of N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): A Selective JAK1 Clinical Candidate for the Treatment of Autoimmune Diseases. PDB 6BBU, 6BBV. Vazquez, M.L., Kaila, N., Strohbach, J.W., Trzupek, J.D., Brown, M.F., Flanagan, M.E., Mitton-Fry, M.J., Johnson, T.A., TenBrink, R.E., Arnold, E.P., Basak, A., Heasley, S.E., Kwon, S., Langille, J., Parikh, M.D., Griffin, S.H., Casavant, J.M., Duclos, B.A., Fenwick, A.E., Harris, T.M., Han, S., Caspers, N., Dowty, M.E., Yang, X., Banker, M.E., Hegen, M., Symanowicz, P.T., Li, L., Wang, L., Lin, T.H., Jussif, J., Clark, J.D., Telliez, J.B., Robinson, R.P., Unwalla, R. J Med Chem.
  49. Dual Allosteric Inhibition of SHP2 Phosphatase. PDB 6BMY, 6BMR, 6BMV, 6BMU, 6BMX, 6BMW. Fodor, M., Price, E., Wang, P., Lu, H., Argintaru, A., Chen, Z., Glick, M., Hao, H.X., Kato, M., Koenig, R., LaRochelle, J.R., Liu, G., McNeill, E., Majumdar, D., Nishiguchi, G.A., Perez, L.B., Paris, G., Quinn, C.M., Ramsey, T., Sendzik, M., Shultz, M.D., Williams, S.L., Stams, T., Blacklow, S.C., Acker, M.G., LaMarche, M.J. ACS Chem Biol.
  50. The Loss of Expression of a Single Type 3 Effector (CT622) Strongly ReducesChlamydia trachomatisInfectivity and Growth. PDB 5UE0. Cosse, M.M., Barta, M.L., Fisher, D.J., Oesterlin, L.K., Niragire, B., Perrinet, S., Millot, G.A., Hefty, P.S., Subtil, A. Front Cell Infect Microbiol.
  51. Fragment-based discovery of a potent NAMPT inhibitor. PDB 5WI0. Korepanova, A., Longenecker, K.L., Pratt, S.D., Panchal, S.C., Clark, R.F., Lake, M., Gopalakrishnan, S.M., Raich, D., Sun, C., Petros, A.M. Bioorg Med Chem Lett.
  52. Structure-Based Design of Selective Noncovalent CDK12 Inhibitors. PDB 6B3E. Johannes, J.W., Denz, C.R., Su, N., Wu, A., Impastato, A.C., Mlynarski, S., Varnes, J.G., Prince, D.B., Cidado, J., Gao, N., Haddrick, M., Jones, N.H., Li, S., Li, X., Liu, Y., Nguyen, T.B., O’Connell, N., Rivers, E., Robbins, D.W., Tomlinson, R., Yao, T., Zhu, X., Ferguson, A.D., Lamb, M.L., Manchester, J.I., Guichard, S. ChemMedChem.
  53. Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497). PDB 6B3W, 4W2R. Kung, P.P., Bingham, P., Brooun, A., Collins, M., Deng, Y.L., Dinh, D., Fan, C., Gajiwala, K.S., Grantner, R., Gukasyan, H.J., Hu, W., Huang, B., Kania, R., Kephart, S.E., Krivacic, C., Kumpf, R.A., Khamphavong, P., Kraus, M., Liu, W., Maegley, K.A., Nguyen, L., Ren, S., Richter, D., Rollins, R.A., Sach, N., Sharma, S., Sherrill, J., Spangler, J., Stewart, A.E., Sutton, S., Uryu, S., Verhelle, D., Wang, H., Wang, S., Wythes, M., Xin, S., Yamazaki, S., Zhu, H., Zhu, J., Zehnder, L., Edwards, M. J Med Chem.
  54. Structural insights into chemokine CCL17 recognition by antibody M116. PDB 5WK2. Teplyakov, A., Obmolova, G., Gilliland, G.L. Biochem Biophys Rep.
  55. Identification of bicyclic hexafluoroisopropyl alcohol sulfonamides as retinoic acid receptor-related orphan receptor gamma (ROR gamma /RORc) inverse agonists. Employing structure-based drug design to improve pregnane X receptor (PXR) selectivity. PDB 6BN6. Gong, H., Weinstein, D.S., Lu, Z., Duan, J.J., Stachura, S., Haque, L., Karmakar, A., Hemagiri, H., Raut, D.K., Gupta, A.K., Khan, J., Camac, D., Sack, J.S., Pudzianowski, A., Wu, D.R., Yarde, M., Shen, D.R., Borowski, V., Xie, J.H., Sun, H., D’Arienzo, C., Dabros, M., Galella, M.A., Wang, F., Weigelt, C.A., Zhao, Q., Foster, W., Somerville, J.E., Salter-Cid, L.M., Barrish, J.C., Carter, P.H., Dhar, T.G.M. Bioorg Med Chem Lett.
  56. A comparative study of the binding properties, dipeptidyl peptidase-4 (DPP-4) inhibitory activity and glucose-lowering efficacy of the DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin in mice. PDB 6B1O, 6B1E . Berger, J.P., SinhaRoy, R., Pocai, A., Kelly, T.M., Scapin, G., Gao, Y.D., Pryor, K.A.D., Wu, J.K., Eiermann, G.J., Xu, S.S., Zhang, X., Tatosian, D.A., Weber, A.E., Thornberry, N.A., Carr, R.D. Endocrinol Diabetes Metab.
  57. Structural insights into humanization of anti-tissue factor antibody 10H10. PDB 5W06. Teplyakov, A., Obmolova, G., Malia, T.J., Raghunathan, G., Martinez, C., Fransson, J., Edwards, W., Connor, J., Husovsky, M., Beck, H., Chi, E., Fenton, S., Zhou, H., Almagro, J.C., Gilliland, G.L. MAbs.
  58. Crystal structure of Staphylococcus aureus Zn-glyoxalase I: new subfamily of glyoxalase I family. PDB 5KEF. Chirgadze, Y.N., Boshkova, E.A., Battaile, K.P., Mendes, V.G., Lam, R., Chan, T.S.Y., Romanov, V., Pai, E.F., Chirgadze, N.Y. J Biomol Struct Dyn.

Address

IMCA-CAT, Sector 17
Advanced Photon Source
Argonne National Laboratory,
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Contact

Lisa Keefe, PhD
keefe@imca-cat.org