Gibbs Sampler-Based λ-Dynamics and Rao-Blackwell Estimator for Alchemical Free Energy Calculation.
Gibbs Sampler-Based λ-Dynamics and Rao-Blackwell Estimator for Alchemical Free Energy Calculation.
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DOI：
10.1021/acs.jctc.7b00204
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发表时间：
2017-06-13
影响因子：
5.5
通讯作者：
Brooks CL 3rd
中科院分区：
文献类型：
--
作者：
Ding X;Vilseck JZ;Hayes RL;Brooks CL 3rd
λ动力学是炼金术自由能计算的一种广义系综方法。在传统的λ动力学中，炼金开关变量λ被视为0 ~ 1范围内的连续变量，并利用经验估计量来近似自由能。在本文中，我们描述了一种利用吉布斯采样器框架的λ动力学的替代公式，我们称之为吉布斯采样器λ动力学（GSLD）。与传统的λ动力学一样，GSLD可以很容易地扩展到在一次模拟中计算多个配体之间的自由能差。我们还引入了一种新的自由能估计量，即与GSLD结合使用的Rao-Blackwell估计量（RBE）。与现有的经验估计量相比，RBE的优点是RBE是一个无偏估计量，其方差通常小于现有的经验估计量。我们还证明了使用RBE可以推导出多态Bennett接受比（MBAR）方程或无箱加权直方图分析方法（UWHAM）方程。我们通过应用于简单谐波系统以及小分子溶剂化和与蛋白质受体结合的相对自由能的相关计算来说明这种新的自由能计算框架的使用和性能。与传统的炼金术自由能方法相比，我们的发现证明了一致性和改进的性能。
λ-dynamics is a generalized ensemble method for alchemical free energy calculations. In traditional λ-dynamics, the alchemical switch variable λ is treated as a continuous variable ranging from 0 to 1 and an empirical estimator is utilized to approximate the free energy. In the present paper, we describe an alternative formulation of λ-dynamics that utilizes the Gibbs sampler framework which we call Gibbs Sampler λ-dynamics (GSLD). GSLD, like traditional λ-dynamics, can be readily extended to calculate free energy differences between multiple ligands in one simulation. We also introduce a new free energy estimator, the Rao-Blackwell estimator (RBE) for use in conjunction with GSLD. Compared with the current empirical estimator, the advantage of RBE is that RBE is an unbiased estimator and its variance is usually smaller than the current empirical estimator. We also show that the multistate Bennett acceptance ratio (MBAR) equation or the unbinned weighted histogram analysis method (UWHAM) equation can be derived using the RBE. We illustrate the use and performance of this new free energy computational framework by application to a simple harmonic system as well as relevant calculations of small molecule relative free energies of solvation and binding to a protein receptor. Our findings demonstrate consistent and improved performance compared with conventional alchemical free energy methods.
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影响因子：
--
作者：
BLACKWELL, D
通讯作者：
BLACKWELL, D
影响因子：
2.8
作者：
BEUTLER, TC;MARK, AE;VANGUNSTEREN, WF
通讯作者：
VANGUNSTEREN, WF
影响因子：
5.5
作者：
Knight, Jennifer L.;Brooks, Charles L., III
通讯作者：
Brooks, Charles L., III
影响因子：
4.4
作者：
Plattner, Nuria;Doll, J. D.;Gubernatis, J. E.
通讯作者：
Gubernatis, J. E.
影响因子：
5.5
作者：
Best, Robert B.;Zhu, Xiao;Shim, Jihyun;Lopes, Pedro E. M.;Mittal, Jeetain;Feig, Michael;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.