Assessment of multiple binding modes in ligand-protein docking

被引：46

作者：

Källblad, P ^{[1
]}

Mancera, RL ^{[1
]}

Todorov, NP ^{[1
]}

机构：

[1] De Novo Pharmaceut, Cambridge CB4 9ZR, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 13期

关键词：

D O I：

10.1021/jm0498147

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Computational ligand-protein docking is routinely used for binding mode prediction. We have quantified the effect of considering multiple docking solutions on the success rate of obtaining the crystallographic binding mode. By selection of a small set of representatives, the experimentally observed binding mode can be predicted with a higher probability after a ligand-protein docking simulation. The proportion of correctly predicted complexes improved from 69% to 87% when five distinct binding modes were considered.

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收藏

页码：3334 / 3337

页数：4

相关论文

共 27 条

[1] Computational methods to predict binding free energy in ligand-receptor complexes [J].

Ajay ;

Murcko, MA .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (26) :4953-4967

[2] Novel inhibitors of DNA gyrase: 3D structure based biased needle screening, hit validation by biophysical methods, and 3D guided optimization. A promising alternative to random screening [J].

Boehm, HJ ;

Boehringer, M ;

Bur, D ;

Gmuender, H ;

Huber, W ;

Klaus, W ;

Kostrewa, D ;

Kuehne, H ;

Luebbers, T ;

Meunier-Keller, N .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (14) :2664-2674

[3] Consensus scoring: A method for obtaining improved hit rates from docking databases of three-dimensional structures into proteins [J].

Charifson, PS ;

Corkery, JJ ;

Murcko, MA ;

Walters, WP .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (25) :5100-5109

[4]

Feynman R. P., 1965, QUANTUM MECH PATH IN

[5] MOLECULAR RECOGNITION OF THE INHIBITOR AG-1343 BY HIV-1 PROTEASE - CONFORMATIONALLY FLEXIBLE DOCKING BY EVOLUTIONARY PROGRAMMING [J].

GEHLHAAR, DK ;

VERKHIVKER, GM ;

REJTO, PA ;

SHERMAN, CJ ;

FOGEL, DB ;

FOGEL, LJ ;

FREER, ST .

CHEMISTRY & BIOLOGY, 1995, 2 (05) :317-324

[6] Ligand-protein docking: Cancer research at the interface between biology and chemistry [J].

Glen, RC ;

Allen, SC .

CURRENT MEDICINAL CHEMISTRY, 2003, 10 (09) :763-777

[7] Protein folding simulations in a deformed energy landscape [J].

Hansmann, UHE .

EUROPEAN PHYSICAL JOURNAL B, 1999, 12 (04) :607-611

[8] QXP: Powerful, rapid computer algorithms for structure-based drug design [J].

McMartin, C ;

Bohacek, RS .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1997, 11 (04) :333-344

[9] Application of the stochastic tunneling method to high throughput database screening [J].

Merlitz, H ;

Burghardt, B ;

Wenzel, W .

CHEMICAL PHYSICS LETTERS, 2003, 370 (1-2) :68-73

[10] Comparison of stochastic optimization methods for receptor-ligand docking [J].

Merlitz, H ;

Wenzel, W .

CHEMICAL PHYSICS LETTERS, 2002, 362 (3-4) :271-277