A model binding site for testing scoring functions in molecular docking.
Abstract
Prediction of interaction energies between ligands and their receptors remains a major challenge for structure-based inhibitor discovery. Much effort has been devoted to developing scoring schemes that can successfully rank the affinities of a diverse set of possible ligands to a binding site for which the structure is known. To test these scoring functions, well-characterized experimental systems can be very useful. Here, mutation-created binding sites in T4 lysozyme were used to investigate how the quality of atomic charges and solvation energies affects molecular docking. Atomic charges and solvation energies were calculated for 172,118 molecules in the Available Chemicals Directory using a semi-empirical quantum mechanical approach by the program AMSOL. The database was first screened against the apolar cavity site created by the mutation Leu99Ala (L99A). Compared to the electronegativity-based charges that are widely used, the new charges and desolvation energies improved ranking of known apolar ligands, and better distinguished them from more polar isosteres that are not observed to bind. To investigate whether the new charges had predictive value, the non-polar residue Met102, which forms part of the binding site, was changed to the polar residue glutamine. The structure of the resulting Leu99Ala and Met102Gln double mutant of T4 lysozyme (L99A/M102Q) was determined and the docking calculation was repeated for the new site. Seven representative polar molecules that preferentially docked to the polar versus the apolar binding site were tested experimentally. All seven bind to the polar cavity (L99A/M102Q) but do not detectably bind to the apolar cavity (L99A). Five ligand-bound structures of L99A/M102Q were determined by X-ray crystallography. Docking predictions corresponded to the crystallographic results to within 0.4A RMSD. Improved treatment of partial atomic charges and desolvation energies in database docking appears feasible and leads to better distinction of true ligands. Simple model binding sites, such as L99A and its more polar variants, may find broad use in the development and testing of docking algorithms.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The development of scoring functions adapted for flexible receptor docking is crucial to achieve real improvements in pose and affinity prediction.
“In this context, the development of scoring functions adapted for flexible receptor docking is crucial to achieve real improvements in pose and affinity prediction (Totrov and Abagyan, 1997; Wei et al., 2002; Fischer et al., 2014; Ravindranath et al., 2015; Lam et al., 2017; Kong et al., 2018).”
From Empirical scoring functions for structure-based virtual screening: applications, critical aspects, and challenges (2018) · cites this paper as Wei et al., 2002
Cites
A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules
Cornell, W. D., Cieplak, P., Bayly, C. I., Gould, I. R., Merz, K. M., Ferguson, D. M., Spellmeyer, D. C., Fox, T., Caldwell, J. W., & Kollman, P. A. (1995) · Journal of the American Chemical Society · doi:10.1021/ja00124a002 · Cited by 13,111 · see citing works
Rapid and efficient site-specific mutagenesis without phenotypic selection.
Kunkel, T. A. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.2.488 · Cited by 7,309 · see citing works
Development and validation of a genetic algorithm for flexible docking 1 1Edited by F. E. Cohen
Jones, G., Willett, P., Glen, R. C., Leach, A. R., & Taylor, R. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0897 · Cited by 6,763 · see citing works
[19] Rapid and efficient site-specific mutagenesis without phenotypic selection
Kunkel, T. A., Roberts, J. D., & Zakour, R. A. (1987) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(87)54085-x · Cited by 5,341 · see citing works
Iterative partial equalization of orbital electronegativity—a rapid access to atomic charges
Gasteiger, J., & Marsili, M. (1980) · Tetrahedron · doi:10.1016/0040-4020(80)80168-2 · Cited by 4,157 · see citing works
Rapid measurement of binding constants and heats of binding using a new titration calorimeter
Wiseman, T., Williston, S., Brandts, J. F., & Lin, L. (1989) · Analytical Biochemistry · doi:10.1016/0003-2697(89)90213-3 · Cited by 2,677 · see citing works
Analytical molecular surface calculation
Connolly, M. L. (1983) · Journal of Applied Crystallography · doi:10.1107/s0021889883010985 · Cited by 2,536 · see citing works
A geometric approach to macromolecule-ligand interactions
Kuntz, I. D., Blaney, J. M., Oatley, S. J., Langridge, R., & Ferrin, T. E. (1982) · Journal of Molecular Biology · doi:10.1016/0022-2836(82)90153-x · Cited by 2,287 · see citing works
Accurate Calculation of Hydration Free Energies Using Macroscopic Solvent Models
Sitkoff, D. F., Sharp, K. A., & Honig, B. H. (1994) · The Journal of Physical Chemistry · doi:10.1021/j100058a043 · Cited by 2,160 · see citing works
Fast, efficient generation of high-quality atomic charges. AM1-BCC model: I. Method
Jakalian, A., Bush, B. L., Jack, D. B., & Bayly, C. I. (2000) · Journal of Computational Chemistry · doi:10.1002/(sici)1096-987x(20000130)21:2 · Cited by 1,695 · see citing works
Continuum Solvent Studies of the Stability of DNA, RNA, and Phosphoramidate−DNA Helices
Srinivasan, J., Cheatham, T. E., Cieplak, P., Kollman, P. A., & Case, D. A. (1998) · Journal of the American Chemical Society · doi:10.1021/ja981844+ · Cited by 1,634 · see citing works
Nicholls, A. O., & Honig, B. H. (1991) · Journal of Computational Chemistry · doi:10.1002/jcc.540120405 · Cited by 1,272 · see citing works
A new method for predicting binding affinity in computer-aided drug design
Åqvist, J., Medina, C., & Samuelsson, J.-E. (1994) · Protein Engineering Design and Selection · doi:10.1093/protein/7.3.385 · Cited by 1,187 · see citing works
Qiu, D., Shenkin, P. S., Hollinger, F. P., & Still, W. C. (1997) · The Journal of Physical Chemistry A · doi:10.1021/jp961992r · Cited by 962 · see citing works
Automated docking with grid‐based energy evaluation
Meng, E. C., Shoichet, B. K., & Kuntz, I. D. (1992) · Journal of Computational Chemistry · doi:10.1002/jcc.540130412 · Cited by 956 · see citing works
Self-citationFerrin, T. E., Huang, C. C., Jarvis, L. E., & Langridge, R. (1988) · Journal of Molecular Graphics · doi:10.1016/0263-7855(88)80054-7 · Cited by 950 · see citing works
An efficient general-purpose least-squares refinement program for macromolecular structures
Tronrud, D. E., Eyck, L. F. T., & Matthews, B. W. (1987) · Acta Crystallographica Section A Foundations of Crystallography · doi:10.1107/s0108767387099124 · Cited by 854 · see citing works
Self-citationÖsterberg, F., Morris, G. M., Sanner, M. F., Olson, A. J., & Goodsell, D. S. (2002) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.10028 · Cited by 474 · see citing works
Gómez, J., Hilser, V. J., Xie, D., & Freire, E. (1995) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340220410 · Cited by 429 · see citing works
Molecular docking using shape descriptors
Shoichet, B. K., Kuntz, I. D., & Bodian, D. L. (1992) · Journal of Computational Chemistry · doi:10.1002/jcc.540130311 · Cited by 428 · see citing works
Self-citationHarvey, S. C., Tan, R. K. ‐., & Cheatham, T. E. (1998) · Journal of Computational Chemistry · doi:10.1002/(sici)1096-987x(199805)19:7 · Cited by 399 · see citing works
Model for Aqueous Solvation Based on Class IV Atomic Charges and First Solvation Shell Effects
Chambers, C. C., Hawkins, G. D., Cramer, C. J., & Truhlar, D. G. (1996) · The Journal of Physical Chemistry · doi:10.1021/jp9610776 · Cited by 360 · see citing works
Structure-Based Discovery of Inhibitors of Thymidylate Synthase
Shoichet, B. K., Stroud, R. M., Santi, D. V., Kuntz, I. D., & Perry, K. M. (1993) · Science · doi:10.1126/science.8451640 · Cited by 323 · see citing works
Self-citationDiscovery of Small-Molecule Inhibitors of Bcl-2 through Structure-Based Computer Screening
Enyedy, I. J., Ling, Y., Nacro, K., Tomita, Y. A., Wu, X., Cao, Y., Guo, R., Li, B., Zhu, X., Huang, Y. K., et al. (2001) · Journal of Medicinal Chemistry · doi:10.1021/jm010016f · Cited by 315 · see citing works
Field, M. J., Albe, M., Bret, C., Martin, F. P.-D., & Thomas, A. M. (2000) · Journal of Computational Chemistry · doi:10.1002/1096-987x(200009)21:12 · Cited by 303 · see citing works
Flexible ligand docking using conformational ensembles
Lorber, D. M., & Shoichet, B. K. (1998) · Protein Science · doi:10.1002/pro.5560070411 · Cited by 294 · see citing works
Self-citationRing, C. S., Sun, E., McKerrow, J. H., Lee, G., Rosenthal, P. J., Kuntz, I. D., & Cohen, F. E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.8.3583 · Cited by 269 · see citing works
A cavity-containing mutant of T4 lysozyme is stabilized by buried benzene
Sauer-Eriksson, A. E., Baase, W. A., Wozniak, J. A., & Matthews, B. W. (1992) · Nature · doi:10.1038/355371a0 · Cited by 266 · see citing works
Self-citationNew Class IV Charge Model for Extracting Accurate Partial Charges from Wave Functions
Li, J., Zhu, T., Cramer, C. J., & Truhlar, D. G. (1998) · The Journal of Physical Chemistry A · doi:10.1021/jp972682r · Cited by 260 · see citing works
Fast, efficient generation of high-quality atomic charges
Jakalian, A. (2000) · Spectrum Research Repository (Concordia University) · Cited by 254 · see citing works
DesJarlais, R. L., Seibel, G., Kuntz, I. D., Furth, P. S., Alvarez, J. C., de Montellano, P. R. O., DeCamp, D. L., Babé, L. M., & Craik, C. S. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.17.6644 · Cited by 253 · see citing works
Inclusion of Solvation in Ligand Binding Free Energy Calculations Using the Generalized-Born Model
Zou, X., Yaxiong, & Kuntz, I. D. (1999) · Journal of the American Chemical Society · doi:10.1021/ja984102p · Cited by 214 · see citing works
Control of Enzyme Activity by an Engineered Disulfide Bond
Matsumura, M., & Matthews, B. W. (1989) · Science · doi:10.1126/science.2916125 · Cited by 213 · see citing works
Self-citationMorton, A., & Matthews, B. W. (1995) · Biochemistry · doi:10.1021/bi00027a007 · Cited by 200 · see citing works
Self-citationEnergetic origins of specificity of ligand binding in an interior nonpolar cavity of T4 lysozyme
Morton, A., Baase, W. A., & Matthews, B. W. (1995) · Biochemistry · doi:10.1021/bi00027a006 · Cited by 184 · see citing works
Self-citationStatistical potentials and scoring functions applied to protein–ligand binding
Gohlke, H., & Klebe, G. (2001) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(00)00195-0 · Cited by 181 · see citing works
A simple method for the calculation of hydration enthalpies of polar molecules with arbitrary shapes
Rashin, A. A., & Namboodiri, K. (1987) · The Journal of Physical Chemistry · doi:10.1021/j100307a038 · Cited by 175 · see citing works
Exhaustive docking of molecular fragments with electrostatic solvation
Majeux, N., Scarsi, M., Apostolakis, J., Ehrhardt, C., & Caflisch, A. (1999) · Proteins Structure Function and Bioinformatics · doi:10.1002/(sici)1097-0134(19991001)37:1 · Cited by 175 · see citing works
Hydration phenomena, classical electrostatics, and the boundary element method
Rashin, A. A. (1990) · The Journal of Physical Chemistry · doi:10.1021/j100368a005 · Cited by 171 · see citing works
Virtual screening with solvation and ligand-induced complementarity
Schnecke, V., & Kuhn, L. A. (2000) · Perspectives in Drug Discovery and Design · doi:10.1023/a:1008737207775 · Cited by 166 · see citing works
A New Ultrasensitive Scanning Calorimeter
Plotnikov, V., Brandts, J. M., Lin, L., & Brandts, J. F. (1997) · Analytical Biochemistry · doi:10.1006/abio.1997.2236 · Cited by 158 · see citing works
The Binding Database: data management and interface design
Chen, X., Lin, Y., Liu, M., & Gilson, M. K. (2002) · Bioinformatics · doi:10.1093/bioinformatics/18.1.130 · Cited by 158 · see citing works
[27] Multiwire area X-ray diffractometers
Hamlin, R. C. (1985) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(85)14029-2 · Cited by 157 · see citing works
Ligand−Protein DataBase: Linking Protein−Ligand Complex Structures to Binding Data
Roche, O., Kiyama, R., & Brooks, C. L. (2001) · Journal of Medicinal Chemistry · doi:10.1021/jm000467k · Cited by 132 · see citing works
New Linear Interaction Method for Binding Affinity Calculations Using a Continuum Solvent Model
Zhou, R., Friesner, R. A., Ghosh, A., Rizzo, R. C., Jorgensen, W. L., & Levy, R. M. (2001) · The Journal of Physical Chemistry B · doi:10.1021/jp011480z · Cited by 122 · see citing works
The inclusion of electrostatic hydration energies in molecular mechanics calculations
Gilson, M. K., & Honig, B. H. (1991) · Journal of Computer-Aided Molecular Design · doi:10.1007/bf00173467 · Cited by 118 · see citing works
Sippl, W. (2000) · Journal of Computer-Aided Molecular Design · doi:10.1023/a:1008115913787 · Cited by 115 · see citing works
Pang, Y., Perola, E., Xu, K., & Prendergast, F. G. (2001) · Journal of Computational Chemistry · doi:10.1002/jcc.1129 · Cited by 106 · see citing works
Poteete, A. R., Daopin, S., Nicholson, H., & Matthews, B. W. (1991) · Biochemistry · doi:10.1021/bi00219a037 · Cited by 101 · see citing works
Self-citationEfficient electrostatic solvation model for protein-fragment docking
Majeux, N., Scarsi, M., & Caflisch, A. (2000) · Proteins Structure Function and Bioinformatics · doi:10.1002/1097-0134(20010201)42:2 · Cited by 97 · see citing works
On the Probability of Finding a Water Molecule in a Nonpolar Cavity
Wolfenden, R., & Radzicka, A. (1994) · Science · doi:10.1126/science.8052849 · Cited by 91 · see citing works
Improved Scoring of Ligand−Protein Interactions Using OWFEG Free Energy Grids
Pearlman, D. A., & Charifson, P. S. (2001) · Journal of Medicinal Chemistry · doi:10.1021/jm000375v · Cited by 89 · see citing works
Inhibitors of Kinesin Activity from Structure-Based Computer Screening
Hopkins, S. C., Vale, R. D., & Kuntz, I. D. (2000) · Biochemistry · doi:10.1021/bi992474k · Cited by 81 · see citing works
Grädler, U., Gerber, H., Goodenough-Lashua, D. M., Garcia, G. A., Ficner, R., Reuter, K., Stubbs, M. T., & Klebe, G. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4256 · Cited by 77 · see citing works
Are membrane proteins ?inside-out? proteins?
Stevens, T. J., & Arkin, I. T. (1999) · Proteins Structure Function and Bioinformatics · doi:10.1002/(sici)1097-0134(19990701)36:1 · Cited by 77 · see citing works
Using CONCORD to construct a large database of three-dimensional coordinates from connection tables
Rusinko, A., Sheridan, R. P., Nilakantan, R., Haraki, K. S., Bauman, N., & Venkataraghavan, R. (1989) · Journal of Chemical Information and Computer Sciences · doi:10.1021/ci00064a004 · Cited by 73 · see citing works
Phage T4 lysozyme Physical properties and reversible unfolding
Elwell, M. L., & Schellman, J. A. (1975) · Biochimica et Biophysica Acta (BBA) - Protein Structure · doi:10.1016/0005-2795(75)90273-1 · Cited by 72 · see citing works
The discovery of steroids and other novel FKBP inhibitors using a molecular docking program
Burkhard, P., Hommel, U., Sanner, M. F., & Walkinshaw, M. D. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2621 · Cited by 65 · see citing works
Tertiary and quaternary conformational changes in aspartate transcarbamylase: a normal mode study
Thomas, A. M., Hinsen, K., Field, M. J., & Pérahia, D. (1999) · Proteins Structure Function and Bioinformatics · doi:10.1002/(sici)1097-0134(19990101)34:1 · Cited by 64 · see citing works
Context‐dependent protein stabilization by methionine‐to‐leucine substitution shown in T4 lysozyme
Lipscomb, L. A., Gassner, N. C., Snow, S. D., Eldridge, A. M., Baase, W. A., Drew, D. L., & Matthews, B. W. (1998) · Protein Science · doi:10.1002/pro.5560070326 · Cited by 53 · see citing works
Self-citationUse of NMR to Detect Water Within Nonpolar Protein Cavities
Matthews, B. W., Morton, A. G., & Dahlquist, F. W. (1995) · Science · doi:10.1126/science.270.5243.1847 · Cited by 51 · see citing works
Self-citationWray, J. W., Baase, W. A., Lindstrom, J. D., Weaver, L. H., Poteete, A. R., & Matthews, B. W. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3102 · Cited by 49 · see citing works
Self-citationHammarström, L., Liljefors, T., & Gasteiger, J. (1988) · Journal of Computational Chemistry · doi:10.1002/jcc.540090418 · Cited by 42 · see citing works
Modifications of the scoring function in FlexX for virtual screening applications
Ståhl, M. (2000) · Perspectives in Drug Discovery and Design · doi:10.1023/a:1008724921888 · Cited by 29 · see citing works
Kirchhoff, W. H. (1993) · doi:10.6028/nist.tn.1401 · Cited by 29 · see citing works
Park, J. M., No, K. T., Jhon, M. S., & Scheraga, H. A. (1993) · Journal of Computational Chemistry · doi:10.1002/jcc.540141210 · Cited by 28 · 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
Modifications of the scoring function in FlexX for virtual screening applications
Ståhl, M. (2005) · Kluwer Academic Publishers eBooks · doi:10.1007/0-306-46883-2_6 · Cited by 15 · see citing works
Flagged first, then by citations
2 of the 70 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Friesner, R. A., Banks, J. L., Murphy, R. B., Halgren, T. A., Klicic, J. J., Mainz, D. T., Repasky, M. P., Knoll, E. H., Shelley, M., Perry, J. K., et al. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm0306430 · Cited by 10,057 · see citing works
Friesner, R. A., Murphy, R. B., Repasky, M. P., Frye, L. L., Greenwood, J. R., Halgren, T. A., Sanschagrin, P. C., & Mainz, D. T. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm051256o · Cited by 6,964 · see citing works
Docking and scoring in virtual screening for drug discovery: methods and applications
Kitchen, D. B., Decornez, H. Y., Furr, J. R., & Bajorath, J. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1549 · Cited by 4,245 · see citing works
ZINC − A Free Database of Commercially Available Compounds for Virtual Screening
Irwin, J. J., & Shoichet, B. K. (2005) · Journal of Chemical Information and Modeling · doi:10.1021/ci049714+ · Cited by 4,058 · see citing works
Self-citationZINC 15 – Ligand Discovery for Everyone
Sterling, T., & Irwin, J. J. (2015) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5b00559 · Cited by 3,224 · see citing works
ZINC: A Free Tool to Discover Chemistry for Biology
Irwin, J. J., Sterling, T., Mysinger, M. M., Bolstad, E. S. D., & Coleman, R. G. (2012) · Journal of Chemical Information and Modeling · doi:10.1021/ci3001277 · Cited by 2,533 · see citing works
Virtual screening of chemical libraries
Shoichet, B. K. (2004) · Nature · doi:10.1038/nature03197 · Cited by 1,425 · see citing works
Self-citationPrinciples and Applications of Halogen Bonding in Medicinal Chemistry and Chemical Biology
Wilcken, R., Zimmermann, M. O., Lange, A., Joerger, A. C., & Boeckler, F. M. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm3012068 · Cited by 1,364 · see citing works
Benchmarking sets for molecular docking.
Huang, N., Shoichet, B. K., & Irwin, J. J. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm0608356 · Cited by 1,318 · see citing works
Self-citationUltra-large library docking for discovering new chemotypes
Lyu, J., Wang, S., Balius, T. E., Singh, I., Levit, A., Moroz, Y. S., O’Meara, M. J., Che, T., Algaa, E., Tolmachova, K., et al. (2019) · Nature · doi:10.1038/s41586-019-0917-9 · Cited by 998 · see citing works
Self-citationCalculation of Protein-Ligand Binding Affinities
Gilson, M. K., & Zhou, H. (2007) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.36.040306.132550 · Cited by 966 · see citing works
Integration of virtual and high-throughput screening
Bajorath, J. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd941 · Cited by 935 · see citing works
DOCK 6: Impact of New Features and Current Docking Performance
Allen, W. J., Balius, T. E., Mukherjee, S., Brozell, S., Moustakas, D., Lang, P. T., Case, D., Kuntz, I., & Rizzo, R. C. (2015) · Journal of Computational Chemistry · doi:10.1002/jcc.23905 · Cited by 731 · see citing works
Advances and Challenges in Protein-Ligand Docking
Huang, S., & Zou, X. (2010) · International Journal of Molecular Sciences · doi:10.3390/ijms11083016 · Cited by 645 · see citing works
Computations of Standard Binding Free Energies with Molecular Dynamics Simulations
Deng, Y., & Roux, B. (2009) · Journal of Physical Chemistry B · doi:10.1021/jp807701h · Cited by 545 · see citing works
A practical guide to large-scale docking
Bender, B. J., Gahbauer, S., Luttens, A., Lyu, J., Webb, C. M., Stein, R. M., Fink, E. A., Balius, T. E., Carlsson, J., Irwin, J. J., et al. (2021) · Nature Protocols · doi:10.1038/s41596-021-00597-z · Cited by 546 · see citing works
“Atomic desolvation energies for ligand atoms are calculated during ligand building using AMSOL 111 and are included in the ligand conformer library.”
MethodSelf-citationHuang, S.-Y., Grinter, S. Z., & Zou, X. (2010) · Physical Chemistry Chemical Physics · doi:10.1039/c0cp00151a · Cited by 508 · see citing works
Lead discovery using molecular docking
Shoichet, B. K., McGovern, S. L., Wei, B. Q., & Irwin, J. J. (2002) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(02)00339-3 · Cited by 508 · see citing works
Self-citationAssessing Scoring Functions for Protein−Ligand Interactions
Ferrara, P., Gohlke, H., Price, D. J., Klebe, G., & Brooks, C. L. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm030489h · Cited by 481 · see citing works
Predicting Binding Free Energies: Frontiers and Benchmarks
Mobley, D. L., & Gilson, M. K. (2017) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-070816-033654 · Cited by 396 · see citing works
Binding MOAD (Mother Of All Databases)
Hu, L., Benson, M. L., Smith, R. D., Lerner, M. G., & Carlson, H. A. (2005) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.20512 · Cited by 328 · see citing works
Guedes, I. A., Pereira, F. S. S., & Dardenne, L. E. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01089 · Cited by 331 · see citing works
Rapid Context-Dependent Ligand Desolvation in Molecular Docking
Mysinger, M. M., & Shoichet, B. K. (2010) · Journal of Chemical Information and Modeling · doi:10.1021/ci100214a · Cited by 323 · see citing works
Self-citationPeng, S., Xiao, W., Ju, D., Sun, B., Hou, N., Liu, Q., Wang, Y., Zhao, H., Gao, C., Zhang, S., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aau7116 · Cited by 317 · see citing works
Mobley, D. L., Chodera, J. D., & Dill, K. A. (2006) · The Journal of Chemical Physics · doi:10.1063/1.2221683 · Cited by 316 · see citing works
ZINC-22─A Free Multi-Billion-Scale Database of Tangible Compounds for Ligand Discovery
Tingle, B. I., Tang, K. G., Castanon, M., Gutierrez, J. J., Khurelbaatar, M., Dandarchuluun, C., Moroz, Y. S., & Irwin, J. J. (2023) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.2c01253 · Cited by 314 · see citing works
Predicting Absolute Ligand Binding Free Energies to a Simple Model Site
Mobley, D. L., Graves, A. P., Chodera, J. D., McReynolds, A. C., Shoichet, B. K., & Dill, K. A. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.06.002 · Cited by 310 · see citing works
Self-citationCalculation of Standard Binding Free Energies: Aromatic Molecules in the T4 Lysozyme L99A Mutant
Deng, Y., & Roux, B. (2006) · Journal of Chemical Theory and Computation · doi:10.1021/ct060037v · Cited by 289 · see citing works
Structure-based discovery of β 2 -adrenergic receptor ligands
Kolb, P., Rosenbaum, D. M., Irwin, J. J., Fung, J. J., Kobilka, B. K., & Shoichet, B. K. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812657106 · Cited by 288 · see citing works
Self-citationDocking Screens for Novel Ligands Conferring New Biology
Irwin, J. J., & Shoichet, B. K. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b02008 · Cited by 281 · see citing works
Self-citationMcGovern, S. L., & Shoichet, B. K. (2003) · Journal of Medicinal Chemistry · doi:10.1021/jm0300330 · Cited by 276 · see citing works
Self-citationStructure-based activity prediction for an enzyme of unknown function
Hermann, J. C., Martí‐Arbona, R., Fedorov, A. A., Fedorov, E. V., Almo, S. C., Shoichet, B. K., & Raushel, F. M. (2007) · Nature · doi:10.1038/nature05981 · Cited by 256 · see citing works
Self-citationBespoke library docking for 5-HT2A receptor agonists with antidepressant activity
Kaplan, A. L., Confair, D. N., Kim, K., Barros-Álvarez, X., Rodriguiz, R. M., Ying, Y., Kweon, O. S., Che, T., McCorvy, J. D., Kamber, D. N., et al. (2022) · Nature · doi:10.1038/s41586-022-05258-z · Cited by 249 · see citing works
Self-citationComplementarity Between a Docking and a High-Throughput Screen in Discovering New Cruzain Inhibitors
Ferreira, R. S., Simeonov, A. M., Jadhav, A., Eidam, O., Mott, B. T., Keiser, M. J., McKerrow, J. H., Maloney, D. J., Irwin, J. J., & Shoichet, B. K. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100488w · Cited by 253 · see citing works
Self-citationMolecular mechanics methods for predicting protein–ligand binding
Huang, N., Kalyanaraman, C., Bernacki, K., & Jacobson, M. P. (2006) · Physical Chemistry Chemical Physics · doi:10.1039/b608269f · Cited by 241 · see citing works
Soft Docking and Multiple Receptor Conformations in Virtual Screening
Ferrari, A. M., Wei, B. Q., Costantino, L., & Shoichet, B. K. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm049756p · Cited by 239 · see citing works
Self-citationProtein–ligand binding with the coarse-grained Martini model
Souza, P. C. T., Thallmair, S., Conflitti, P., Ramírez-Palacios, C., Alessandri, R., Raniolo, S., Limongelli, V., & Marrink, S. (2020) · Nature Communications · doi:10.1038/s41467-020-17437-5 · Cited by 201 · see citing works
Cao, Y., & Li, L. (2014) · Bioinform. · doi:10.1093/bioinformatics/btu104 · Cited by 201 · see citing works
Structure-Based Discovery of A 2A Adenosine Receptor Ligands
Carlsson, J., Yoo, L. S., Gao, Z.-G., Irwin, J. J., Shoichet, B. K., & Jacobson, K. A. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100240h · Cited by 229 · see citing works
Self-citationLigand Pose and Orientational Sampling in Molecular Docking
Coleman, R. G., Carchia, M., Sterling, T., Irwin, J. J., & Shoichet, B. K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075992 · Cited by 223 · see citing works
Self-citationSun, L., Wang, Y., & Miao, M. (2020) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2020.08.003 · Cited by 221 · see citing works
Huang, S., & Zou, X. (2006) · Journal of Computational Chemistry · doi:10.1002/jcc.20504 · Cited by 215 · see citing works
Lessons from the lysozyme of phage T4
Baase, W. A., Liu, L., Tronrud, D. E., & Matthews, B. W. (2010) · Protein Science · doi:10.1002/pro.344 · Cited by 199 · see citing works
Self-citationChapter 4 Alchemical Free Energy Calculations: Ready for Prime Time?
Shirts, M., Mobley, D., & Chodera, J. (2007) · Annual reports in computational chemistry · doi:10.1016/s1574-1400(07)03004-6 · Cited by 157 · see citing works
Diazepam-bound GABAA receptor models identify new benzodiazepine binding-site ligands
Richter, L., de Graaf, C., Sieghart, W., Varagić, Z., Mörzinger, M., de Esch, I. J. P., Ecker, G. F., & Ernst, M. C. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.917 · Cited by 197 · see citing works
Rescoring docking hit lists for model cavity sites: predictions and experimental testing.
Graves, A. P., Shivakumar, D., Boyce, S. E., Jacobson, M., Case, D., & Shoichet, B. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.01.049 · Cited by 184 · see citing works
Self-citationPredicting ligand binding affinity with alchemical free energy methods in a polar model binding site
Boyce, S. E., Mobley, D., Rocklin, G., Graves, A. P., Dill, K., & Shoichet, B. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.09.049 · Cited by 180 · see citing works
Self-citationTesting a Flexible-receptor Docking Algorithm in a Model Binding Site
Wei, B. Q., Weaver, L. H., Ferrari, A. M., Matthews, B. W., & Shoichet, B. K. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.02.015 · Cited by 179 · see citing works
Self-citationFragment Based Drug Design: From Experimental to Computational Approaches
Kumar, A., Voet, A. R. D., & Zhang, K. Y. J. (2012) · Current Medicinal Chemistry · doi:10.2174/092986712803530467 · Cited by 170 · see citing works
Wereszczynski, J., & McCammon, J. (2011) · Quarterly Reviews of Biophysics (print) · doi:10.1017/s0033583511000096 · Cited by 152 · see citing works
Gallicchio, E., Lapelosa, M., & Levy, R. M. (2010) · Journal of Chemical Theory and Computation · doi:10.1021/ct1002913 · Cited by 158 · see citing works
Towards accurate free energy calculations in ligand protein-binding studies.
Steinbrecher, T., & Labahn, A. (2010) · Current Medicinal Chemistry · doi:10.2174/092986710790514453 · Cited by 161 · see citing works
Applications of large-scale density functional theory in biology
Cole, D. J., & Hine, N. (2016) · Journal of Physics: Condensed Matter · doi:10.1088/0953-8984/28/39/393001 · Cited by 149 · see citing works
Fischer, M., Coleman, R. G., Fraser, J. S., & Shoichet, B. K. (2014) · Nature Chemistry · doi:10.1038/nchem.1954 · Cited by 149 · see citing works
Self-citationMolecular Docking Screens Using Comparative Models of Proteins
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
Self-citationProperty-Unmatched Decoys in Docking Benchmarks
Stein, R. M., Ying, Y., Balius, T. E., O’Meara, M. J., Lyu, J., Young, J., Tang, K. G., Shoichet, B. K., & Irwin, J. J. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c00598 · Cited by 136 · see citing works
Self-citationHuang, S., & Zou, X. (2010) · Journal of Chemical Information and Modeling · doi:10.1021/ci9002987 · Cited by 136 · see citing works
Docking Screens: Right for the Right Reasons?
Kolb, P., & Irwin, J. J. (2009) · Current Topics in Medicinal Chemistry · doi:10.2174/156802609789207091 · Cited by 132 · see citing works
Virtual Screening against Metalloenzymes for Inhibitors and Substrates
Irwin, J. J., Raushel, F. M., & Shoichet, B. K. (2005) · Biochemistry · doi:10.1021/bi050801k · Cited by 121 · see citing works
Self-citationScoring functions for protein–ligand interactions: a critical perspective
Schulz‐Gasch, T., & Ståhl, M. (2004) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2004.08.004 · Cited by 120 · see citing works
Recent Theoretical and Computational Advances for Modeling Protein-Ligand Binding Affinities
Gallicchio, E., & Levy, R. (2011) · Advances in Protein Chemistry and Structural Biology · doi:10.1016/b978-0-12-386485-7.00002-8 · Cited by 112 · see citing works
Rastelli, G., Degliesposti, G., Río, A. D., & Sgobba, M. (2009) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2009.00780.x · Cited by 116 · see citing works
Wang, K., Chodera, J., Yang, Y., & Shirts, M. (2013) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-013-9689-8 · Cited by 115 · see citing works
Novel Ligands for a Purine Riboswitch Discovered by RNA-Ligand Docking
Daldrop, P., Reyes, F. E., Robinson, D. A., Hammond, C. M., Lilley, D. M. J., Batey, R., & Brenk, R. (2011) · Chemistry & Biology · doi:10.1016/j.chembiol.2010.12.020 · Cited by 112 · see citing works
Mapping the Hydration Dynamics of Ubiquitin
Nucci, N. V., Pometun, M. S., & Wand, A. J. (2011) · Journal of the American Chemical Society · doi:10.1021/ja202033k · Cited by 109 · see citing works
Decoys Selection in Benchmarking Datasets: Overview and Perspectives
Réau, M. F., Langenfeld, F., Zagury, J., Lagarde, N., & Montès, M. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00011 · Cited by 108 · see citing works
Mpamhanga, C. P., Spinks, D., Tulloch, L. B., Shanks, E. J., Robinson, D. A., Collie, I. T., Fairlamb, A. H., Wyatt, P. G., Frearson, J. A., Hunter, W. N., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm900414x · Cited by 105 · see citing works
Ferrari, A. M., Degliesposti, G., Sgobba, M., & Rastelli, G. (2007) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2007.08.019 · Cited by 105 · see citing works
Graves, A. P., Brenk, R., & Shoichet, B. K. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm0491187 · Cited by 105 · see citing works
Self-citationStructure-based discovery of conformationally selective inhibitors of the serotonin transporter
Singh, I., Seth, A., Billesbølle, C. B., Bráz, J. M., Rodriguiz, R. M., Roy, K., Bekele, B., Craik, V., Huang, X., Boytsov, D., et al. (2023) · Cell · doi:10.1016/j.cell.2023.04.010 · Cited by 99 · see citing works
Self-citationDrug Design: Free-energy calculations in structure-based drug design
Shirts, M., Mobley, D., & Brown, S. P. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511730412.007 · Cited by 60 · see citing works
Liu, L., Baase, W. A., & Matthews, B. W. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.10.086 · Cited by 87 · see citing works
Self-citationSoelaiman, S., Wei, B. Q., Bergson, P., Lee, Y., Shen, Y., Mrksich, M., Shoichet, B. K., & Tang, W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301232200 · Cited by 86 · see citing works
Self-citationKing, J. T., Arthur, E. J., Brooks, C. L., & Kubarych, K. J. (2012) · The Journal of Physical Chemistry B · doi:10.1021/jp300835k · Cited by 80 · see citing works
Guo, Z., Li, B., Cheng, L., Zhou, S., McCammon, J. A., & Che, J. (2015) · Journal of Chemical Theory and Computation · doi:10.1021/ct500867u · Cited by 78 · see citing works
Sensitivity in Binding Free Energies Due to Protein Reorganization
Lim, N. M., Wang, L., Abel, R., & Mobley, D. L. (2016) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.6b00532 · Cited by 73 · see citing works
Lee, H., Fischer, M. M., Shoichet, B. K., & Liu, S. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b06566 · Cited by 75 · see citing works
Self-citationPathak, R. K., Gupta, A., Shukla, R., & Baunthiyal, M. (2018) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2018.05.015 · Cited by 75 · see citing works
Lin, X., Huang, X.-P., Chen, G., Whaley, R., Peng, S., Wang, Y., Zhang, G., Wang, S. X., Wang, S., Roth, B. L., et al. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm300338m · Cited by 73 · see citing works
Relative Binding Free Energy Calculations Applied to Protein Homology Models
Cappel, D., Hall, M., Lenselink, E. B., Beuming, T., Qi, J., Bradner, J., & Sherman, W. (2016) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.6b00362 · Cited by 64 · see citing works
Korczynska, M., Clark, M. J., Valant, C., Xu, J. Z., Moo, E. V., Albold, S., Weiss, D. R., Torosyan, H., Huang, W., Kruse, A. C., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1718037115 · Cited by 71 · see citing works
Self-citationSystematic Evaluation of Counterpoise Correction in Density Functional Theory
Gray, M., Bowling, P. E., & Herbert, J. M. (2022) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.2c00883 · Cited by 68 · see citing works
Probing Molecular Docking in a Charged Model Binding Site
Brenk, R., Vetter, S. W., Boyce, S. E., Goodin, D. B., & Shoichet, B. K. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.01.034 · Cited by 65 · see citing works
Self-citationConformational Transitions and Convergence of Absolute Binding Free Energy Calculations
Lapelosa, M., Gallicchio, E., & Levy, R. (2012) · Journal of Chemical Theory and Computation · doi:10.1021/ct200684b · Cited by 60 · see citing works
Escape of a Small Molecule from Inside T4 Lysozyme by Multiple Pathways.
Nunes-Alves, A., Zuckerman, D., & Arantes, G. M. (2018) · Biophysical Journal · doi:10.1016/j.bpj.2018.01.014 · Cited by 67 · see citing works
Binding-Site Assessment by Virtual Fragment Screening
Huang, N., & Jacobson, M. P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010109 · Cited by 60 · see citing works
Fox, S. J., Pittock, C., Fox, T., Tautermann, C. S., Malcolm, N. O. J., & Skylaris, C. (2011) · The Journal of Chemical Physics · doi:10.1063/1.3665893 · Cited by 60 · see citing works
Foloppe, N., Chen, I., Davis, B. J., Hold, A., Morley, D., & Howes, R. (2004) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2003.12.023 · Cited by 58 · see citing works
Urich, R., Wishart, G., Kiczun, M., Richters, A., Tidten, N., Rauh, D., Sherborne, B. S., Wyatt, P. G., & Brenk, R. (2013) · ACS Chemical Biology · doi:10.1021/cb300729y · Cited by 52 · see citing works
Homologous ligands accommodated by discrete conformations of a buried cavity
Merski, M., Fischer, M. M., Balius, T. E., Eidam, O., & Shoichet, B. K. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1500806112 · Cited by 52 · see citing works
Self-citationEngineering a model protein cavity to catalyze the Kemp elimination
Merski, M., & Shoichet, B. K. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208076109 · Cited by 51 · see citing works
Self-citationFox, S., Dziedzic, J., Fox, T., Tautermann, C., & Skylaris, C.-K. (2014) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.24686 · Cited by 43 · see citing works
Gundelach, L., Fox, T., Tautermann, C. S., & Skylaris, C. (2021) · Physical Chemistry Chemical Physics · doi:10.1039/d1cp00206f · Cited by 49 · see citing works
Structure-Based Discovery of Inhibitors of the SARS-CoV-2 Nsp14 N7-Methyltransferase
Singh, I., Li, F., Fink, E. A., Chau, I., Li, A. S. M., Rodríguez‐Hernández, A., Glenn, I., Belinchón, F. J. Z., Rodriguez, M. L., Devkota, K., et al. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c02120 · Cited by 49 · see citing works
Self-citationAn effective docking strategy for virtual screening based on multi-objective optimization algorithm
Li, H., Zhang, H., Zheng, M., Luo, J., Kang, L., Liu, X., Wang, X., & Jiang, H. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-58 · Cited by 49 · see citing works
Physics-based methods for studying protein-ligand interactions.
Huang, N., & Jacobson, M. P. (2007) · PubMed · Cited by 48 · see citing works
Pathak, R. K., Baunthiyal, M., Shukla, R., Pandey, D., Taj, G., & Kumar, A. (2017) · Frontiers in Plant Science · doi:10.3389/fpls.2017.00609 · Cited by 47 · see citing works
Large‐scale DFT calculations in implicit solvent—A case study on the T4 lysozyme L99A/M102Q protein
Dziedzic, J., Fox, S. J., Fox, T., Tautermann, C. S., & Skylaris, C. (2012) · International Journal of Quantum Chemistry · doi:10.1002/qua.24075 · Cited by 45 · see citing works
Recent Advances in Computer-Aided Drug Design as Applied to Anti-Influenza Drug Discovery
Mallipeddi, P. L., Kumar, G., White, S. W., & Webb, T. R. (2014) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026614666140929153812 · Cited by 44 · see citing works
Lipids Regulate Lck Protein Activity through Their Interactions with the Lck Src Homology 2 Domain
Sheng, R., Jung, D.-J., Silkov, A., Kim, H., Singaram, I., Wang, Z.-G., Xin, Y., Kim, E., Park, M.-J., Thiagarajan-Rosenkranz, P., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.720284 · Cited by 43 · see citing works
- Authors
- Wei, B. Q., Baase, W. A., Weaver, L. H., Matthews, B. W., & Shoichet, B. K.
- Affiliations
- Northwestern University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Matthews, Brian W.
- Shoichet, Brian K.
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2002-09
- Volume
- 322
- Issue
- 2
- Pages
- 339-355
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W1980285986
- Cited by
- 237
- References
- 70
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 9 · 2023: 14 · 2022: 8 · 2021: 10 · 2020: 10 · 2019: 16 · 2018: 11 · 2017: 8 · 2016: 13 · 2015: 10 · 2014: 10 · 2013: 9 · 2012: 15
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Northwestern University
- National Institutes of Health
- National Institute of General Medical Sciences (GM-21967, GM59957, R01GM059957, R01GM021967)
- Topics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Advanced Chemical Physics Studies
- Keywords
- molecular docking, scoring functions, T4 lysozyme, atomic charges, desolvation energy, solvation energy, ligand binding affinity, partial atomic charges, ligand ranking
- MeSH terms
- Algorithms, Binding Sites, Calorimetry, Ligands, Models, Molecular, Muramidase, Mutation, Protein Binding, Protein Conformation, Software, Databases, Factual, Bacteriophage T4, Crystallography, X-Ray, Amino Acid Substitution, Hydrophobic and Hydrophilic Interactions
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 ›
Are you an author, or do you see a problem with this page? Request a review
