THE WEIGHTED HISTOGRAM ANALYSIS METHOD FOR FREE-ENERGY CALCULATIONS ON BIOMOLECULES .1. THE METHOD
THE WEIGHTED HISTOGRAM ANALYSIS METHOD FOR FREE-ENERGY CALCULATIONS ON BIOMOLECULES .1. THE METHOD
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DOI：
10.1002/jcc.540130812
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发表时间：
1992-10-01
影响因子：
3
通讯作者：
ROSENBERG, JM
中科院分区：
文献类型：
--
作者：
KUMAR, S;BOUZIDA, D;ROSENBERG, JM
加权直方图分析法（WHAM）是Ferrenberg和Swendsen的多重直方图技术的一种推广，首次应用于复杂生物分子的哈密顿量。这里提出的方法作为伞抽样法的自由能和平均力的计算潜力的扩展。该算法与目前采用的方法相比具有以下优点：（1）它提供了采样误差的内建估计，从而产生为达到所需精度水平所需的附加模拟的最佳位置和长度的客观估计;（2）它通过考虑所有模拟来产生自由能的“最佳”值，从而使统计误差最小化;（3）除了优化模拟之间的联系之外，它还允许概率分布的多次重叠，以获得自由能差的更好估计。通过将Ferrenberg-Swendsen多重直方图方程改写为适合于分子力学型哈密顿量的形式，并将其应用于生成脱氧腺苷糖环伪旋转相位角的平均力势分布的测试问题，证明了该方法的可行性和鲁棒性.
The Weighted Histogram Analysis Method (WHAM), an extension of Ferrenberg and Swendsen's Multiple Histogram Technique, has been applied for the first time on complex biomolecular Hamiltonians. The method is presented here as an extension of the Umbrella Sampling method for free-energy and Potential of Mean Force calculations. This algorithm possesses the following advantages over methods that are currently employed: (1) It provides a built-in estimate of sampling errors thereby yielding objective estimates of the optimal location and length of additional simulations needed to achieve a desired level of precision; (2) it yields the "best" value of free energies by taking into account all the simulations so as to minimize the statistical errors; (3) in addition to optimizing the links between simulations, it also allows multiple overlaps of probability distributions for obtaining better estimates of the free-energy differences. By recasting the Ferrenberg-Swendsen Multiple Histogram equations in a form suitable for molecular mechanics type Hamiltonians, we have demonstrated the feasibility and robustness of this method by applying it to a test problem of the generation of the Potential of Mean Force profile of the pseudorotation phase angle of the sugar ring in deoxyadenosine.