Predictions of binding of a diverse set of ligands to gelatinase-A by a   combination of molecular dynamics and continuum solvent models

doi:10.1021/jp015516z

CORC > 北京大学 > 化学与分子工程学院

	Predictions of binding of a diverse set of ligands to gelatinase-A by a combination of molecular dynamics and continuum solvent models
	Hou, TJ ; Guo, SL ; Xu, XJ
刊名	journal of physical chemistry b
	2002
关键词	FREE-ENERGY CALCULATIONS SELECTIVE INHIBITORS GENETIC ALGORITHMS LINEAR-RESPONSE DRUG DESIGN FORCE-FIELD MATRIX AFFINITIES SIMULATIONS COMPLEXES
DOI	10.1021/jp015516z
英文摘要	The free energies of binding, DeltaG(bind), between a diverse set of eight hydroxamate inhibitors with gelatinase-A (MMP-2) were computed by using the recently developed MM/PBSA approach. In this paper, a nonbonded model was used to represent the potentials of the catalytic zinc center. Molecular dynamics (MD) simulations were used to generate the thermally averaged ensemble of conformations of the ligand-protein complexes. On the basis of the trajectories from MD simulations, the free energies of binding were calculated using molecular mechanics, the continuum solvent model, surface area estimation, and normal-mode analysis. The results show that MM/PBSA not only can rank the studied ligands effectively but also can reproduce the experimental binding free energies successfully. The predicted binding free energies correlate well with the experimental values (r = 0.84, q = 0.78). As a comparison, the free energies of binding were also computed by using the linear interaction energy approximation (LIE). The overall agreement between the calculated and experimental values for the diverse set of ligands means that the MM/PBSA approach is a useful tool for the general evaluation of protein-ligand interactions. The analysis of the separate energy terms contributing to MM/PBSA free energy indicates that the association between hydroxamate and MMP-2 is mainly driven by more favorable van der Waals/nonpolar interactions in the complex than in solution.; Chemistry, Physical; SCI(E); EI; 73; ARTICLE; 21; 5527-5535; 106
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/388261]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Hou, TJ,Guo, SL,Xu, XJ. Predictions of binding of a diverse set of ligands to gelatinase-A by a combination of molecular dynamics and continuum solvent models[J]. journal of physical chemistry b,2002.
APA	Hou, TJ,Guo, SL,&Xu, XJ.(2002).Predictions of binding of a diverse set of ligands to gelatinase-A by a combination of molecular dynamics and continuum solvent models.journal of physical chemistry b.
MLA	Hou, TJ,et al."Predictions of binding of a diverse set of ligands to gelatinase-A by a combination of molecular dynamics and continuum solvent models".journal of physical chemistry b (2002).