| Record 8543 View: Standard | Glossary HistCite Guide |
|
Author(s): Spyrakis F (Spyrakis, Francesca); Amadasi A (Amadasi, Alessio); Fornabaio M (Fornabaio, Micaela); Abraham DJ (Abraham, Donald J.); Mozzarelli A (Mozzarelli, Andrea); Kellogg GE (Kellogg, Glen E.); Cozzini P (Cozzini, Pietro)
Title: The consequences of scoring docked ligand conformations using free energy correlations
Source: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 42 (7): 921-933
Date: 2007 JUL
Document Type: Journal : Article
DOI: 10.1016/j.ejmech.2006.12.037
Language: English
Comment:
Address: Virginia Commonwealth Univ, Inst Struct Biol & Drug Discovery, Dept Med Chem, Richmond, VA 23298 USA.
Univ Parma, Dept Biochem & Mol Biol, I-43100 Parma, Italy. Univ Parma, Dept Gen & Inorgan Chem, I-43100 Parma, Italy. Reprint: Kellogg, GE, Virginia Commonwealth Univ, Inst Struct Biol & Drug
Discovery, Dept Med Chem, Med Coll Virginia Campus, Richmond, VA 23298 USA. E-mail: glen.kellogg@vcu.edu
pictro.cozzini@unipr.it Author Keywords: HINTS; docking; free energy scoring; hydropathic analysis
KeyWords Plus: INCREMENTAL CONSTRUCTION ALGORITHM; ARABINOSE-BINDING PROTEIN; CRYSTAL-
STRUCTURES; DRUG DESIGN; INTUITIVE CALCULATIONS; AUTOMATED DOCKING;
GENETIC ALGORITHM; 3-DIMENSIONAL STRUCTURES; THROMBIN INHIBITORS;
STRUCTURAL-ANALYSIS
Abstract: Ligands from a set of 19 protein-ligand complexes were re-docked with AutoDock, GOLD and FlexX using the scoring algorithms native to these programs supplemented by analysis using the HINT free energy force field. A HINT scoring function was calibrated for this data set using a simple linear regression of total HINT score for crystal-structure complexes vs. measured free energy of binding. This function had an r(2) of 0.84 and a standard error of 0.42 kcal mol(-1). The free energies of binding were calculated for the best poses using the AutoDock, GOLD and FlexX scoring, functions. The AutoDock and GoIdScore algorithms estimated more than half of the binding free energies within the reported calibration standard errors for these functions, while that of FlexX did not. In contrast, the calibrated HINT scoring function identified optimized poses with standard errors near +/- 0.5 kcal mol(-1). When the metric of success is minimum RMSD (vs. crystallographic coordinates) the three docking programs were more successful, with mean RMSDs for the top-ranking poses in the 19 complexes of 3.38, 2.52 and 2.62 angstrom for AntoDock, GOLD and FlexX, respectively. Two key observations in this study have general relevance for computational medicinal chemistry: first, while optimizing RMSD with docking score functions is clearly of value, these functions may be less well optimized for free energy of binding, which has broader applicability in virtual screening and drug discovery than RMSD; second, scoring functions uniquely calibrated for the data set or sets under stud), should nearly always be preferable to universal scoring functions. Due to these advantages, the poses selected by the HINT score also required less post-docking structure optimization to produce usable molecular models. Most of these features may be achievable with other scoring functions. (c) 2007 Elsevier Masson SAS. All rights reserved.
Cited References: ABAGYAN R, 1994, J COMPUT CHEM, V15, P488 AMADASI A, 2006, J MOL BIOL, V358, P289, DOI 10.1016/j.jmb.2006.01.053 AMARI G, 2004, BIOORGAN MED CHEM, V12, P3763, DOI 10.1016/j.bmc.2004.05.015 BADGER J, 1988, P NATL ACAD SCI USA, V85, P3304 BADGER J, 1989, PROTEINS, V6, P1 BERMAN HM, 2000, NUCLEIC ACIDS RES, V28, P235 BISSANTZ C, 2000, J MED CHEM, V43, P4759 BOHM HJ, 1994, J COMPUT AID MOL DES, V8, P243 BOREK D, 2003, ACTA CRYSTALLOGR 11, V59, P2031, DOI 10.1107/S0907444903020924 BRANDSTETTER H, 1992, J MOL BIOL, V226, P1085 BURNETT JC, 2000, BIOCHEMISTRY-US, V39, P1622 BURNETT JC, 2001, PROTEINS, V42, P355 BURSULAYA BD, 2003, J COMPUT AID MOL DES, V17, P755 CARD GL, 2005, NAT BIOTECHNOL, V23, P201, DOI 10.1038/nbt1059 CHARIFSON PS, 1999, J MED CHEM, V42, P5100 CHARIFSON PS, 2002, J COMPUT AID MOL DES, V16, P311 CHEN HM, 2006, J CHEM INF MODEL, V46, P401, DOI 10.1021/ci0503255 CHIRGADZE NY, 2000, PROTEIN SCI, V9, P29 CLARK RD, 2002, J MOL GRAPH MODEL, V20, P281 COLE JC, 2005, PROTEINS, V60, P325, DOI 10.1002/prot.20497 COZZINI P, 2002, J MED CHEM, V45, P2469 COZZINI P, 2004, CURR MED CHEM, V11, P3093 DAVIS AM, 2003, ANGEW CHEM INT EDIT, V42, P2718, DOI 10.1002/anie.200200539 DEREWENDA ZS, 1995, J MOL BIOL, V252, P248 EALICK SE, 1991, P NATL ACAD SCI USA, V88, P11540 FERRARA P, 2004, J MED CHEM, V47, P3032, DOI 10.1021/jm030489h FORNABAIO M, 2003, J MED CHEM, V46, P4487, DOI 10.1021/jm0302593 FORNABAIO M, 2004, J MED CHEM, V47, P4507, DOI 10.1021/jm030596b FRIESNER RA, 2004, J MED CHEM, V47, P1739, DOI 10.1021/jm0306430 GIBSON AL, 1988, PROTEINS, V3, P155 GOHLKE H, 2000, J MOL BIOL, V295, P337 GOODFORD PJ, 1985, J MED CHEM, V28, P849 GOODSELL DS, 1990, PROTEINS, V8, P195 GUDDAT LW, 1994, J MOL BIOL, V236, P247 HA S, 2000, J COMPUT AID MOL DES, V14, P435 HOFFMANN D, 1999, J MED CHEM, V42, P4422 HUAI Q, 2003, STRUCTURE, V11, P865, DOI 10.1016/S0969-2126(03)00123-0 JONES G, 1995, J MOL BIOL, V245, P43 JONES G, 1997, J MOL BIOL, V267, P727 KELLENBERGER E, 2004, PROTEINS, V57, P225, DOI 10.1002/prot.20149 KELLOGG GE, 1992, MED CHEM RES, V1, P444 KELLOGG GE, 1999, MED CHEM RES, V9, P439 KELLOGG GE, 2000, EUR J MED CHEM, V35, P651 KLEYWEGT GJ, 1994, STRUCTURE, V2, P1241 KONTOYIANNI M, 2004, J MED CHEM, V47, P558, DOI 10.1021/jm0302997 KRAMER B, 1999, PROTEINS, V37, P228 KROEMER RT, 2004, J CHEM INF COMP SCI, V44, P871, DOI 10.1021/ci049970m LALONDE JM, 1994, BIOCHEMISTRY-US, V33, P4885 LYBRAND TP, 1995, CURR OPIN STRUC BIOL, V5, P224 MAKINO S, 1997, J COMPUT CHEM, V18, P1812 MCMARTIN C, 1997, J COMPUT AID MOL DES, V11, P333 MILLER DM, 1983, J BIOL CHEM, V258, P3665 MORRIS GM, 1996, J COMPUT AID MOL DES, V10, P293 MORRIS GM, 1998, J COMPUT CHEM, V19, P1639 PEREZ C, 2001, J MED CHEM, V44, P3768 PEROLA E, 2004, PROTEINS, V56, P235, DOI 10.1002/prot.20088 POROTTO M, 2006, J VIROL, V80, P1204, DOI 10.1128/JVI.80.3.1204-1213.2006 QUIOCHO FA, 1984, NATURE, V310, P381 RADIC Z, 1991, MOL PHARMACOL, V39, P98 RAREY M, 1996, J MOL BIOL, V261, P470 RAVELLI RBG, 1998, ACTA CRYSTALLOGR D 6, V54, P1359 RICHIERI GV, 1994, J BIOL CHEM, V269, P23918 SALL DJ, 1997, J MED CHEM, V40, P3489 SCAPIN G, 2004, BIOCHEMISTRY-US, V43, P6091, DOI 10.1021/bi049868i SCHULZGASCH T, 2003, J MOL MODEL, V9, P47, DOI 10.1007/s00894-002-0112-y SHIAU AK, 1998, CELL, V95, P927 SIEGENTHALER G, 1992, BIOCHEM J, V287, P383 SOUNESS JE, 2000, IMMUNOPHARMACOLOGY, V47, P127 STAHL M, 1998, J MOL GRAPH MODEL, V16, P121 STAHL M, 2001, J MED CHEM, V44, P1035 STURZEBECHER J, 1984, THROMB RES, V36, P457 TERP GE, 2001, J MED CHEM, V44, P2333 TURK D, 1991, FEBS LETT, V287, P133 VARGAS R, 2000, J AM CHEM SOC, V122, P4750 VERDONK ML, 2003, PROTEINS, V52, P609, DOI 10.1002/prot.10465 VERMERSCH PS, 1991, BIOCHEMISTRY-US, V30, P6861 VYAS NK, 1988, SCIENCE, V242, P1290 WALTERS WP, 1998, DRUG DISCOV TODAY, V3, P160 WANG J, 1999, PROTEINS, V36, P1 WANG RX, 2002, J COMPUT AID MOL DES, V16, P11 WANG RX, 2003, J MED CHEM, V46, P2287, DOI 10.1021/jm0203783 WANG RX, 2004, J CHEM INF COMP SCI, V44, P2114, DOI 10.1021/ci049733j WARREN GL, 2006, J MED CHEM, V49, P5912, DOI 10.1021/jm050362n WHITLOW M, 1995, PROTEIN ENG, V8, P749 XING L, 2004, J COMPUT AID MOL DES, V18, P333 XU ZH, 1993, J BIOL CHEM, V268, P7874 |