文献类型：期刊文章

作　　者：李鹏飞[1] 贾相瑜[1,2] 王美婷[1] 梅晔[1,2,3]

机构地区：[1]华东师范大学物理与材料科学学院精密光谱科学与技术国家重点实验室,上海200062 [2]华东师范大学-上海纽约大学计算化学联合中心,上海200062 [3]俄克拉荷马大学化学和生物化学系,诺曼73019

出　　处：《Chinese Journal of Chemical Physics》

年　　份：2017

卷　　号：30

期　　号：6

起止页码：789-799

语　　种：中文

收录情况：0、AJ、CAS、CSCD、CSCD2017_2018、INSPEC、JST、RSC、SCIE、SCOPUS、ZGKJHX、普通刊

摘　　要：Estimation of protein-ligand binding affinity within chemical accuracy is one of the grand challenges in structure-based rational drug design. With the efforts over three decades, free energy methods based on equilibrium molecular dynamics （MD） simulations have become mature and are nowadays routinely applied in the community of computational chemistry. On the contrary, nonequilibrinm MD simulation methods have attracted less attention, despite their underlying rigor in mathematics and potential advantage in efficiency. In this work, the equilibrium and nonequilibrium simulation methods are compared in terms of accuracy and convergence rate in the calculations of relative binding free energies. The proteins studied are T4-lysozyme mutant L99A and COX-2. For each protein, two ligands are studied. The results show that the noneqnilibrium simulation method can be competitively as accurate as the equilibrium method, and the former is more efficient than the latter by considering the convergence rate with respect to the cost of wall clock time. In addition, Bennett acceptance ratio, which is a bidirectional post-processing method, converges faster than the unidirectional Jarzynski equality for the nonequilibrium simulations.

关 键 词：Free energy  EQUILIBRIUM NONEQUILIBRIUM Convergence rate  ACCURACY

分 类 号：O]