Calculation of free-energy differences by confinement simulations. Application to peptide conformers.
Calculation of free-energy differences by confinement simulations. Application to peptide conformers.
复制标题
DOI：
10.1021/jp9020646
复制
发表时间：
2009-07-23
期刊：
影响因子：
--
通讯作者：
Karplus M
中科院分区：
文献类型：
--
作者：
Cecchini M;Krivov SV;Spichty M;Karplus M
构象自由能差异是理解分子生物学中涉及大分子结构变化的重要现象的关键量。在本文中，一个改进的版本的限制方法，这是基于早期的发展，确定的自由能的个别国家逐步限制的分子构象纯谐波盆地，其绝对自由能可以计算的正常模式分析。该方法被用来计算在真空中的丙氨酸二肽的两个结构已知的分子状态之间的自由能差，和蛋白质G的β-发夹与隐式溶剂化模型。在所有的情况下，禁闭的结果是在良好的协议从平衡分子动力学模拟，其中有一个更大的计算成本。确定了结果的系统误差和统计误差，并确定了误差的来源。计算的自由能差异的分子状态的结构为基础的定义的敏感性进行了讨论。的方法，它关闭的准谐波，而不是谐波分析的热力学循环的一个变种，提出。后者提出了明确的溶剂模拟可能使用。
Conformational free-energy differences are key quantities for understanding important phenomena in molecular biology that involve large structural changes of macromolecules. In this paper, an improved version of the confinement approach, which is based on earlier developments, determines the free energy of the individual states by progressively restraining the molecular conformations to pure harmonic basins, whose absolute free energy can be computed by normal-mode analysis. The method is used to calculate the free-energy difference between two structurally known molecular states of the alanine dipeptide in vacuo, and the β-hairpin from protein G with an implicit solvation model. In all cases, the confinement results are in excellent agreement with the ones obtained from equilibrium molecular dynamics simulations, which have a much larger computational cost. The systematic and statistical errors of the results are determined and the origin of the errors is identified. The sensitivity of the calculated free-energy differences to structure-based definitions of molecular states is discussed. A variant of the method, which closes the thermodynamic cycle by a quasi-harmonic rather than harmonic analysis, is proposed. The latter is proposed for possible use with explicit solvent simulations.
登录
查看更多内容
DOI：
10.1073/pnas.0800228105
发表时间：
2008-09-16
影响因子：
11.1
作者：
Krivov, Sergei V.;Karplus, Martin
通讯作者：
Karplus, Martin
影响因子：
4.4
作者：
FRENKEL, D;LADD, AJC
通讯作者：
LADD, AJC
影响因子：
56.9
作者：
Boehr, David D.;McElheny, Dan;Wright, Peter E.
通讯作者：
Wright, Peter E.
影响因子：
3.3
作者：
Krivov, Sergei V.;Karplus, Martin
通讯作者：
Karplus, Martin
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M