Computing Alchemical Free Energy Differences with Hamiltonian Replica Exchange Molecular Dynamics (H-REMD) Simulations.
Computing Alchemical Free Energy Differences with Hamiltonian Replica Exchange Molecular Dynamics (H-REMD) Simulations.
复制标题
使用哈密顿复制品交换分子动力学（H-REMD）模拟计算炼金术自由能差。
DOI：
10.1021/ct200153u
复制
发表时间：
2011-09-13
影响因子：
5.5
通讯作者：
Roitberg, Adrian E.
中科院分区：
文献类型：
--
作者：
Meng, Yilin;Dashti, Danial Sabri;Roitberg, Adrian E.
炼金术自由能计算在分子建模领域起着非常重要的作用。人们已经努力提高这些计算的准确性和精密度。其中一项努力是采用哈密顿副本交换分子动力学（H - REMD）方法来增强构象采样。在本文中，我们证明了HREMD方法不仅提高了炼金术自由能计算的收敛性，而且还可通过自由能微扰（FEP）算法直接用于计算自由能差值。我们展示了H - REMD和常用的FEP方程之间的直接映射，然后直接用它们来计算自由能。H - REMD炼金术自由能计算（副本交换自由能微扰，REFEP）在预测硫氧还蛋白中包埋的天冬氨酸26（Asp26）的pKa值上进行了测试。我们将REFEP的结果与热力学积分（TI）和常规FEP模拟的结果进行了比较。REFEP计算比TI和常规FEP模拟收敛得更快。H - REMD模拟最终预测的pKa值也非常准确，仅比实验值高0.4个pKa单位。利用REFEP算法显著改善了构象采样，进而提高了炼金术自由能模拟的收敛性。
Alchemical free energy calculations play a very important role in the field of molecular modeling. Efforts have been made to improve the accuracy and precision of those calculations. One of the efforts is to employ a Hamiltonian replica exchange molecular dynamics (H-REMD) method to enhance conformational sampling. In this paper, we demonstrated that HREMD method not only improves convergence in alchemical free energy calculations but also can be used to compute free energy differences directly via the Free Energy Perturbation (FEP)algorithm. We show a direct mapping between the H-REMD and the usual FEP equations, which are then used directly to compute free energies. The H-REMD alchemical free energy calculation (Replica exchange Free Energy Perturbation, REFEP) was tested on predicting the pKa value of the buried Asp26 in thioredoxin. We compare the results of REFEP with TI and regular FEP simulations. REFEP calculations converged faster than those from TI and regular FEP simulations. The final predicted pKa value from the H-REMD simulation was also very accurate, only 0.4 pKa unit above the experimental value. Utilizing the REFEP algorithm significantly improves conformational sampling, and this in turn improves the convergence of alchemical free energy simulations.
登录
查看更多内容
影响因子：
4.1
作者：
BENNETT, CH
通讯作者：
BENNETT, CH
影响因子：
4.4
作者：
JORGENSEN, WL;RAVIMOHAN, C
通讯作者：
RAVIMOHAN, C
影响因子：
4.1
作者：
MEZEI, M
通讯作者：
MEZEI, M
影响因子：
5.5
作者：
Jorgensen, William L.;Thomas, Laura L.
通讯作者：
Thomas, Laura L.
影响因子：
4.4
作者：
Fukunishi, H;Watanabe, O;Takada, S
通讯作者：
Takada, S