Implications of protein flexibility for drug discovery
Abstract
Proteins are in constant motion between different conformational states with similar energies. This has often been ignored in drug design. However, protein flexibility is fundamental to understanding the ways in which drugs exert biological effects, their binding-site location, binding orientation, binding kinetics, metabolism and transport. Protein flexibility allows increased affinity to be achieved between a drug and its target. This is crucial, because the lipophilicity and number of polar interactions allowed for an oral drug is limited by absorption, distribution, metabolism and toxicology considerations.
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Physic-based methods such as docking can be sensitive to structural error or pocket conformational changes.
“Albeit powerful, due to their heavy dependency on atomic distances to evaluate scoring functions, these methods can be sensitive to structural error or pocket conformational changes 3 .”
From Graph Convolutional Neural Networks for Predicting Drug-Target Interactions (2019) · cites this paper as [3]
Cites
Molecular basis of agonism and antagonism in the oestrogen receptor
Brzozowski, A. M., Pike, A. C. W., Dauter, Z., Hubbard, R. E., Bonn, T., Engström, O., Öhman, L., Greene, G. L., Gustafsson, J.-Å., & Carlquist, M. (1997) · Nature · doi:10.1038/39645 · Cited by 3,355 · see citing works
Shiau, A. K., Barstad, D., Loria, P. M., Cheng, L., Kushner, P. J., Agard, D. A., & Greene, G. L. (1998) · Cell · doi:10.1016/s0092-8674(00)81717-1 · Cited by 2,726 · see citing works
Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents
Kurumbail, R. G., Stevens, A. M., Gierse, J. K., McDonald, J. J., Stegeman, R. A., Pak, J. Y., Gildehaus, D., iyashiro, J. M., Penning, T. D., Seibert, K., et al. (1996) · Nature · doi:10.1038/384644a0 · Cited by 1,922 · see citing works
Structural mechanism for statin inhibition of HMG-CoA reductase
Istvan, E. S., & Deisenhofer, J. (2001) · Science · doi:10.1126/science.1059344 · Cited by 1,644 · see citing works
Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site
Pargellis, C., Tong, L., Churchill, L., Cirillo, P. F., Gilmore, T., Graham, A. G., Grob, P. M., Hickey, E. R., Moss, N., Pav, S., et al. (2002) · Nature Structural Biology · doi:10.1038/nsb770 · Cited by 834 · see citing works
The Human Nuclear Xenobiotic Receptor PXR: Structural Determinants of Directed Promiscuity
Watkins, R. E., Wisely, G. B., Moore, L. B., Collins, J. L., Lambert, M. H., Williams, S. P., Willson, T. M., Kliewer, S. A., & Redinbo, M. R. (2001) · Science · doi:10.1126/science.1060762 · Cited by 760 · see citing works
Kryger, G., Silman, I., & Sussman, J. L. (1999) · Structure · doi:10.1016/s0969-2126(99)80040-9 · Cited by 755 · see citing works
Structural Mechanisms for Domain Movements in Proteins
Gerstein, M., Lesk, A. M., & Chothia, C. (1994) · Biochemistry · doi:10.1021/bi00188a001 · Cited by 741 · see citing works
Enzyme Dynamics During Catalysis
Eisenmesser, E. Z., Bosco, D. A., Akke, M., & Kern, D. (2002) · Science · doi:10.1126/science.1066176 · Cited by 732 · see citing works
A relationship between protein stability and protein function.
Shoichet, B. K., Baase, W. A., Kuroki, R., & Matthews, B. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.2.452 · Cited by 712 · see citing works
Sawaya, M. R., & Kraut, J. (1997) · Biochemistry · doi:10.1021/bi962337c · Cited by 676 · see citing works
Podust, L. M., Poulos, T. L., & Waterman, M. R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061562898 · Cited by 534 · see citing works
Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases
Heightman, T. D., & Vasella, A. T. (1999) · Angewandte Chemie International Edition · doi:10.1002/(sici)1521-3773(19990315)38:6 · Cited by 507 · see citing works
High resolution structures of HIV-1 RT from four RT–inhibitor complexes
Ren, J., Esnouf, R. M., Garman, E. F., Somers, D. O., Ross, C., Kirby, I., Keeling, J., Darby, G. K., Jones, E. Y., Stuart, D. I., et al. (1995) · Nature Structural & Molecular Biology · doi:10.1038/nsb0495-293 · Cited by 503 · see citing works
Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside inhibitors
Esnouf, R. M., Ren, J., Ross, C., Jones, E. Y., STAMMERS, D. K., & Stuart, D. I. (1995) · Nature Structural & Molecular Biology · doi:10.1038/nsb0495-303 · Cited by 442 · see citing works
Structural basis of inhibitor selectivity in MAP kinases
Wang, Z., Canagarajah, B. J., Boehm, J. C., Kassisà, S., Cobb, M. H., Young, P. R., Abdel‐Meguid, S. S., Adams, J. L., & Goldsmith, E. J. (1998) · Structure · doi:10.1016/s0969-2126(98)00113-0 · Cited by 426 · see citing works
Multiple diverse ligands binding at a single protein site: A matter of pre‐existing populations
Ma, B., Shatsky, M., Wolfson, H. J., & Nussinov, R. (2002) · Protein Science · doi:10.1110/ps.21302 · Cited by 420 · see citing works
Binding of small molecules to an adaptive protein–protein interface
Arkin, M. R., Randal, M., DeLano, W. L., Hyde, J., Luong, T. N., Oslob, J. D., Raphael, D. R., Taylor, L., Wang, J., McDowell, R. S., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252756299 · Cited by 376 · see citing works
Structure of acetylcholinesterase complexed with the nootropic alkaloid, (–)-huperzine A
Raves, M. L., Harel, M., Pang, Y., Silman, I., Kozikowski, A. P., & Sussman, J. L. (1997) · Nature Structural & Molecular Biology · doi:10.1038/nsb0197-57 · Cited by 373 · see citing works
Rational design of potent human transthyretin amyloid disease inhibitors.
Sacchettini, J. C., Klabunde, T., Petrassi, H. M., Oza, V. B., Raman, P., & Kelly, J. W. (2000) · Nature Structural Biology · doi:10.1038/74082 · Cited by 373 · see citing works
Structural Mechanisms of QacR Induction and Multidrug Recognition
Schumacher, M. A., Miller, M. C., Grkovic, S., Brown, M. H., Skurray, R. A., & Brennan, R. G. (2001) · Science · doi:10.1126/science.1066020 · Cited by 369 · see citing works
Hopkins, A. L., Ren, J., Esnouf, R. M., Willcox, B. E., Jones, E. Y., Ross, C., Miyasaka, T., Walker, R. T., Tanaka, H., STAMMERS, D. K., et al. (1996) · Journal of Medicinal Chemistry · doi:10.1021/jm960056x · Cited by 349 · see citing works
Smerdon, S. J., Jäger, J., Wang, J., Kohlstaedt, L. A., Chirino, A. J., Friedman, J. M., Rice, P. A., & Steitz, T. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.9.3911 · Cited by 331 · see citing works
Protein flexibility and drug design: how to hit a moving target
Carlson, H. A. (2002) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(02)00341-1 · Cited by 314 · see citing works
Harel, M., Kryger, G., Rosenberry, T. L., Mallender, W. D., Lewis, T., Fletcher, R. J., Guss, J. M., Silman, I., & Sussman, J. L. (2000) · Protein Science · doi:10.1110/ps.9.6.1063 · Cited by 299 · see citing works
Kinetic basis for selective inhibition of cyclo-oxygenases
Gierse, J. K., Koboldt, C. M., Walker, M. C., Seibert, K., & Isakson, P. C. (1999) · Biochemical Journal · doi:10.1042/bj3390607 · Cited by 287 · see citing works
Browner, M. F., Lovejoy, B., Welch, A. R., Carr, S., Luong, C., Broka, C. A., Hendricks, R. T., Campbell, J. A., Walker, K. A. M., Martin, R., et al. (1999) · Nature Structural Biology · doi:10.1038/6657 · Cited by 255 · see citing works
Krebs, W. G. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.8.1665 · Cited by 243 · see citing works
Deciphering common failures in molecular docking of ligand-protein complexes
Verkhivker, G. M., Bouzida, D., Gehlhaar, D. K., Rejto, P. A., Arthurs, S., Colson, A. B., Freer, S. T., Larson, V., Luty, B. A., Marrone, T. J., et al. (2000) · Journal of Computer-Aided Molecular Design · doi:10.1023/a:1008158231558 · Cited by 240 · see citing works
Increased protein backbone conformational entropy upon hydrophobic ligand binding.
Novotný, M. V., Stone, M. J., & Žı́dek, L. (1999) · Nature Structural Biology · doi:10.1038/70057 · Cited by 236 · see citing works
Urzhumtsev, A., Favier, F., Mitschler, A., et al. (1997) · Structure · doi:10.1016/s0969-2126(97)00216-5 · Cited by 233 · see citing works
Schevitz, R. W., Bach, N. J., CARLSON, D. G., Chirgadze, N. Y., Clawson, D. K., Dillard, R. D., Draheim, S. E., Hartley, L. W., Jones, N. D., Mihelich, E. D., et al. (1995) · Nature Structural & Molecular Biology · doi:10.1038/nsb0695-458 · Cited by 216 · see citing works
CRYSTAL STRUCTURES OF METYRAPONE-AND PHENYLIMIDAZOLE-INHIBITED COMPLEXES OF CYTOCHROME P450-CAM
Poulos, T. L., & Howard, A. J. (1987) · Biochemistry · doi:10.1021/bi00399a022 · Cited by 215 · see citing works
Raag, R., & Poulos, T. L. (1990) · Biochemistry · doi:10.1021/bi00224a016 · Cited by 213 · see citing works
Bursavich, M. G., & Rich, D. H. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm010425b · Cited by 208 · see citing works
Morton, A., & Matthews, B. W. (1995) · Biochemistry · doi:10.1021/bi00027a007 · Cited by 200 · see citing works
Baldwin, J. J., Ponticello, G. S., Anderson, P., Christy, M. E., Murcko, M. A., Randall, W. C., Schwam, H., Sugrue, M. F., & Gautheron, P. (1989) · Journal of Medicinal Chemistry · doi:10.1021/jm00132a003 · Cited by 197 · see citing works
Taylor, N. R., Cleasby, A., Singh, O., Skarzynski, T. J., Wonacott, A. J., Smith, P. W., Sollis, S. L., Howes, P. D., Cherry, P. C., Bethell, R. C., et al. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm9703754 · Cited by 193 · see citing works
Kulmacz, R. J., & Lands, W. E. M. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38909-3 · Cited by 190 · see citing works
MolMovDB: analysis and visualization of conformational change and structural flexibility
Echols, N. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg104 · Cited by 190 · see citing works
Agonist-receptor efficacy I: mechanisms of efficacy and receptor promiscuity
Kenakin, T. (1995) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)89020-3 · Cited by 177 · see citing works
Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat.
Wilson, D. K., Tarle, I., Petrash, J. M., et al. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.21.9847 · Cited by 163 · see citing works
Murray, C. W., Baxter, C. A., & Frenkel, A. D. (1999) · Journal of Computer-Aided Molecular Design · doi:10.1023/a:1008015827877 · Cited by 161 · see citing works
Manipulation of ligand binding affinity by exploitation of conformational coupling.
Marvin, J. S., & Hellinga, H. W. (2001) · Nature Structural Biology · doi:10.1038/nsb0901-795 · Cited by 153 · see citing works
Wang, M. Z., Tai, C. Y., & Mendel, D. B. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.12.3809-3816.2002 · Cited by 151 · see citing works
Mechanism of inhibition of cholinesterases by huperzine A
Ashani, Y., Peggins, J. O., & Doctor, B. P. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)90649-6 · Cited by 144 · see citing works
Mayer, C. R., Cabuil, V., Lalot, T., & Thouvenot, R. (1999) · Angewandte Chemie International Edition · doi:10.1002/(sici)1521-3773(19991216)38:24 · Cited by 139 · see citing works
Muzammil, S., Ross, P. A., & Freire, E. (2003) · Biochemistry · doi:10.1021/bi027019u · Cited by 138 · see citing works
A new allosteric site in glycogen phosphorylase b as a target for drug interactions
Oikonomakos, N. G., Skamnaki, V. T., Tsitsanou, K. E., Gavalas, N. G., & Johnson, L. N. (2000) · Structure · doi:10.1016/s0969-2126(00)00144-1 · Cited by 132 · see citing works
Human liver glycogen phosphorylase inhibitors bind at a new allosteric site
Rath, V. L., Ammirati, M. J., Danley, D. E., Ekstrom, J. L., Gibbs, E. M., Hynes, T. R., Mathiowetz, A. M., McPherson, R. K., Olson, T. V., Treadway, J. L., et al. (2000) · Chemistry & Biology · doi:10.1016/s1074-5521(00)00004-1 · Cited by 129 · see citing works
Modi, S. P., Sutcliffe, M. J., Primrose, W. U., Lian, L., & Roberts, G. C. K. (1996) · Nature Structural Biology · doi:10.1038/nsb0596-414 · Cited by 128 · see citing works
Brandstetter, H., Grams, F., Glitz, D., Lang, A., Huber, R., Bode, W., Krell, H., & Engh, R. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007475200 · Cited by 127 · see citing works
Oefner, C., Binggeli, A., Breu, V., Bur, D., Clozel, J.-P., D'Arcy, A., Dorn, A., Fischli, W., Grüninger, F., Güller, R., et al. (1999) · Chemistry & Biology · doi:10.1016/s1074-5521(99)89004-8 · Cited by 126 · see citing works
Rahuel, J. (1991) · Journal of Structural Biology · doi:10.1016/1047-8477(91)90048-2 · Cited by 122 · see citing works
Ren, J., Nichols, C. E., Bird, L. E., Fujiwara, T., Sugimoto, H., Stuart, D. I., & STAMMERS, D. K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.19.14316 · Cited by 121 · see citing works
Conformational Change of Elongation Factor Tu (EF-Tu) Induced by Antibiotic Binding
Vogeley, L., Palm, G. J., Mesters, J. R., & Hilgenfeld, R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100017200 · Cited by 116 · see citing works
Domain Flexibility in Retroviral Proteases: Structural Implications for Drug Resistant Mutations,
Rose, R. B., Craik, C. S., & Stroud, R. M. (1998) · Biochemistry · doi:10.1021/bi9716074 · Cited by 113 · see citing works
Abraham, D. J., Wireko, F. C., Randad, R. S., et al. (1992) · Biochemistry · doi:10.1021/bi00153a005 · Cited by 109 · see citing works
Conformational switching in an aspartic proteinase
Lee, A. Y., Gulnik, S., & Erickson, J. W. (1998) · Nature Structural Biology · doi:10.1038/2306 · Cited by 109 · see citing works
Feng, Y., Likos, J. J., Zhu, L., et al. (2002) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/s0167-4838(02)00307-2 · Cited by 104 · see citing works
Conformational Dynamics along an Enzymatic Reaction Pathway: Thymidylate Synthase, “the Movie”
Stroud, R. M., & Finer-Moore, J. S. (2002) · Biochemistry · doi:10.1021/bi020598i · Cited by 103 · see citing works
Yaremchuk, A. D., Tukalo, M. A., Grøtli, M., et al. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4712 · Cited by 101 · see citing works
Scrofani, S. D. B., Chung, J., Huntley, J. J. A., et al. (1999) · Biochemistry · doi:10.1021/bi990986t · Cited by 99 · see citing works
Inhibitor-induced conformational change in cytochrome P-450CAM
Raag, R., Li, H., Jones, B., & Poulos, T. L. (1993) · Biochemistry · doi:10.1021/bi00068a013 · Cited by 95 · see citing works
Making a Network of Hydrophobic Clusters
Baldwin, R. L. (2002) · Science · doi:10.1126/science.1069893 · Cited by 92 · see citing works
Complexity and simplicity of ligand–macromolecule interactions: the energy landscape perspective
Verkhivker, G. M., Bouzida, D., Gehlhaar, D. K., Rejto, P. A., Freer, S. T., & Rose, P. W. (2002) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(02)00310-x · Cited by 90 · see citing works
Active Site Plasticity in d -Amino Acid Oxidase: A Crystallographic Analysis,
Todone, F., Vanoni, M. A., Mozzarelli, A., et al. (1997) · Biochemistry · doi:10.1021/bi9630570 · Cited by 88 · see citing works
Structure-Based Development of Anticancer Drugs
Faig, M., Bianchet, M. A., Winski, S. L., et al. (2001) · Structure · doi:10.1016/s0969-2126(01)00636-0 · Cited by 83 · see citing works
Wright, S. W., Carlo, A. A., Carty, M. D., Danley, D. E., Hageman, D. L., Karam, G. A., Levy, C. B., Mansour, M. N., Mathiowetz, A. M., McClure, L. D., et al. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm010496a · Cited by 83 · see citing works
Computer simulations of protein folding by targeted molecular dynamics
Ferrara, P., Apostolakis, J., & Caflisch, A. (2000) · Proteins Structure Function and Bioinformatics · doi:10.1002/(sici)1097-0134(20000515)39:3 · Cited by 78 · see citing works
Zographos, S. E., Oikonomakos, N. G., Tsitsanou, K. E., Leonidas, D. D., Chrysina, E. D., Skamnaki, V. T., Bischoff, H., Goldmann, S., Watson, K. A., & Johnson, L. N. (1997) · Structure · doi:10.1016/s0969-2126(97)00292-x · Cited by 77 · see citing works
Raman, C. S., Li, H., Pavel Martasek, E., Southan, G. J., Masters, B. S. S., & Poulos, T. L. (2001) · Biochemistry · doi:10.1021/bi010957u · Cited by 76 · see citing works
SMITH, G. M., Alexander, R., Christianson, D. W., McKeever, B. M., Ponticello, G. S., Springer, J. P., Randall, W. C., Baldwin, J. J., & Habecker, C. N. (1994) · Protein Science · doi:10.1002/pro.5560030115 · Cited by 67 · see citing works
Falke, J. J. (2002) · Science · doi:10.1126/science.1069823 · Cited by 66 · see citing works
Tucker, T. J., Lumma, W. C., Mulichak, A. M., et al. (1997) · Journal of Medicinal Chemistry · doi:10.1021/jm960762y · Cited by 65 · see citing works
Suresh, S., Bressi, J. C., Kennedy, K. J., Verlinde, C. L. M. J., Gelb, M. H., & Hol, W. G. J. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4588 · Cited by 63 · see citing works
Tong, L., Pav, S., Mui, S., Lamarre, D., Yoakim, C., Beaulieu, P. L., & Anderson, P. C. (1995) · Structure · doi:10.1016/s0969-2126(01)00133-2 · Cited by 54 · see citing works
Structure-Based Design of Inhibitors Specific for Bacterial Thymidylate Synthase,
Stout, T. J., Tondi, D., Rinaldi, M., et al. (1999) · Biochemistry · doi:10.1021/bi9815896 · Cited by 52 · see citing works
The application of thermodynamic methods in drug design
Velázquez‐Campoy, A., Luque, I., & Freire, E. (2001) · Thermochimica Acta · doi:10.1016/s0040-6031(01)00671-2 · Cited by 52 · see citing works
Molecular Recognition of Cyclic Urea HIV-1 Protease Inhibitors
Ala, P. J., DeLoskey, R. J., Huston, E. E., Jadhav, P. K., Lam, P. Y. S., Eyermann, C. J., Hodge, C. N., Schadt, M. C., Lewandowski, F. A., Weber, P. C., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.20.12325 · Cited by 43 · see citing works
Brzozowski, A. M., Öhman, L., Pike, A. C. W., et al. (1997) · Cited by 42 · see citing works
Weichsel, A., & Montfort, W. R. (1995) · Nature Structural & Molecular Biology · doi:10.1038/nsb1295-1095 · Cited by 36 · see citing works
Fritz, T. A., Tondi, D., Finer-Moore, J. S., et al. (2001) · Chemistry & Biology · doi:10.1016/s1074-5521(01)00067-9 · Cited by 32 · see citing works
Melnick, M., Reich, S., Lewis, K. K., et al. (1996) · Journal of Medicinal Chemistry · doi:10.1021/jm960092w · Cited by 30 · see citing works
Chirgadze, N. Y., Sall, D. J., Klimkowski, V. J., et al. (1997) · Protein Science · doi:10.1002/pro.5560060705 · Cited by 27 · see citing works
Steegborn, C., Laber, B., Messerschmidt, A., et al. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4880 · Cited by 25 · see citing works
Chirgadze, N. Y., Sall, D. J., Briggs, S., et al. (2000) · Protein Science · doi:10.1110/ps.9.1.29 · Cited by 25 · see citing works
Liggins, J. R., & Privalov, P. L. (2000) · Proteins Structure Function and Bioinformatics · doi:10.1002/1097-0134(2000)41:4+ · Cited by 24 · see citing works
Pouplana, R., Pérez, C., Sánchez, J., et al. (1999) · Journal of Computer-Aided Molecular Design · doi:10.1023/a:1008094616324 · Cited by 18 · see citing works
Building Blocks, Hinge-Bending Motions and Protein Topology
Sinha, N., Tsai, C.-J., & Nussinov, R. (2001) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2001.10506747 · Cited by 13 · see citing works
Graul, A., Leeson, P. A., & Castañer, J. (1999) · Drugs of the Future · doi:10.1358/dof.1999.024.11.555874 · Cited by 10 · see citing works
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Feixas, F., Lindert, S., Sinko, W., & McCammon, J. A. (2014) · Biophysical Chemistry · doi:10.1016/j.bpc.2013.10.007 · Cited by 156 · see citing works
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Fan, H., Irwin, J. J., Webb, B. M., Klebe, G., Shoichet, B. K., & Sali, A. (2009) · Journal of Chemical Information and Modeling · doi:10.1021/ci9003706 · Cited by 135 · see citing works
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Bhandari, B. K., Gardner, P. P., & Lim, C. S. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa578 · Cited by 97 · see citing works
Systematic exploitation of multiple receptor conformations for virtual ligand screening.
Bottegoni, G., Rocchia, W., Rueda, M., Abagyan, R., & Cavalli, A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018845 · Cited by 96 · see citing works
Alexander, C. G., Jürgens, M. C., Shepherd, D. A., Freund, S. M. V., Ashcroft, A. E., & Ferguson, N. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1308846110 · Cited by 85 · see citing works
Protein flexibility in drug discovery: from theory to computation.
Buonfiglio, R., Recanatini, M., & Masetti, M. (2015) · ChemMedChem · doi:10.1002/cmdc.201500086 · Cited by 73 · see citing works
Protein-Protein Interactions as Drug Targets
Wendt, M. D. (2012) · Topics in Medicinal Chemistry · doi:10.1007/978-3-642-28965-1_1 · Cited by 9 · see citing works
- Authors
- Teague, S. J.
- Affiliations
- AstraZeneca (United Kingdom) (GB)
- Corresponding author
- Teague, Simon J.
- Venue
- Nature Reviews Drug Discovery
- Published
- 2003-07
- Volume
- 2
- Issue
- 7
- Pages
- 527-541
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W1974645077
- Cited by
- 755
- References
- 91
- Citations by year
- 2026: 41 · 2025: 29 · 2024: 29 · 2023: 24 · 2022: 18 · 2021: 31 · 2020: 36 · 2019: 16 · 2018: 28 · 2017: 27 · 2016: 32 · 2015: 28 · 2014: 44 · 2013: 32 · 2012: 40
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Keywords
- protein flexibility, protein conformational states, drug-target binding, binding affinity, binding kinetics, binding orientation, binding sites, drug metabolism, drug transport, drug absorption, lipophilicity, polar interactions, drug design
- MeSH terms
- Ligands, Protein Conformation, Thermodynamics, Drug Design
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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