Flexible docking in solution using metadynamics

被引:239
作者
Gervasio, FL [1 ]
Laio, A [1 ]
Parrinello, M [1 ]
机构
[1] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, CH-6900 Lugano, Switzerland
关键词
D O I
10.1021/ja0445950
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
We apply our recently developed metadynamics method to the docking of ligands on flexible receptors in water solution. This method mimics the real dynamics of a ligand exiting or entering an enzyme and in so doing reconstructs the free energy surface. We apply it to four docking cases: beta-trypsin/benzamidine, beta-trypsin/chlorobenzamidine, immunoglobulin McPC-603/phosphocholine, and cyclin-dependent kinase 2/staurosporine. In every case studied, the method is able to predict the docked geometry and the free energy of docking. Its added value with respect to many other available methods is that it reconstructs the complete free energy surface, including all the relevant minima and the barriers between them.
引用
收藏
页码:2600 / 2607
页数:8
相关论文
共 56 条
[31]   Escaping free-energy minima [J].
Laio, A ;
Parrinello, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (20) :12562-12566
[32]   Protein kinase inhibition by staurosporine revealed in details of the molecular interaction with CDK2 [J].
Lawrie, AM ;
Noble, MEM ;
Tunnah, P ;
Brown, NR ;
Johnson, LN ;
Endicott, JA .
NATURE STRUCTURAL BIOLOGY, 1997, 4 (10) :796-801
[33]  
Mangoni R, 1999, PROTEINS, V35, P153, DOI 10.1002/(SICI)1097-0134(19990501)35:2<153::AID-PROT2>3.0.CO
[34]  
2-E
[35]   ELECTRONIC EFFECTS IN INTERACTION OF PARA-SUBSTITUTED BENZAMIDINES WITH TRYPSIN - INVOLVEMENT OF PI-ELECTRONIC DENSITY AT CENTRAL ATOM OF SUBSTITUENT IN BINDING [J].
MARESGUIA, M ;
NELSON, DL ;
ROGANA, E .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1977, 99 (07) :2331-2336
[36]   Theory of biomolecular recognition [J].
McCammon, JA .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 1998, 8 (02) :245-249
[37]   Chemical inhibitors of cyclin-dependent kinases [J].
Meijer, L .
TRENDS IN CELL BIOLOGY, 1996, 6 (10) :393-397
[38]   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
[39]   Comparison of stochastic optimization methods for receptor-ligand docking [J].
Merlitz, H ;
Wenzel, W .
CHEMICAL PHYSICS LETTERS, 2002, 362 (3-4) :271-277
[40]   Reconstructing the density of states by history-dependent metadynamics [J].
Micheletti, C ;
Laio, A ;
Parrinello, M .
PHYSICAL REVIEW LETTERS, 2004, 92 (17) :170601-1