Optimal pairwise and non-pairwise alchemical pathways for free energy calculations of molecular transformation in solution phase
Optimal pairwise and non-pairwise alchemical pathways for free energy calculations of molecular transformation in solution phase
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DOI：
10.1063/1.3697833
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发表时间：
2012-03-28
影响因子：
4.4
通讯作者：
Shirts, Michael R.
中科院分区：
文献类型：
--
作者：
Pham, Tri T.;Shirts, Michael R.
我们估计的全球最小方差路径计算的自由能插入或删除的小分子从稠密流体。我们进行这种优化对所有的潜力，无论功能形式，使用功能优化与两体近似的径向分布函数。令人惊讶的是，通过该方法获得的最佳成对路径几乎与使用Pham和Shirts [J. Chem. Phys. 135，034114（2011）]报道的优化的广义“软核”势获得的路径相同。我们还推导了最小方差的非成对潜在路径的分子插入或删除，并比较其效率的成对路径，在一定条件下，非成对路径可以减少高达60%的总方差相比，最佳的成对路径。然而，最佳的非成对路径一般不出现实际的自由能计算的可行性，因为一个准确的估计的自由能，参数本身是期望的，是需要构建这个非成对path. Additionally，模拟在大多数中间状态的这些非成对路径有显着较长的相关时间，往往超过标准的模拟长度为大体积分子的溶剂化。这些发现表明，以前获得的软核心途径是在实践中的分子插入或缺失的最低变异途径。研究结果还表明，确定与分子模拟进行的热力学过程的效率的功能优化的效用。(C)2012年美国物理学会。[http：//dx.doi.org/10.1063/1.3697833]
We estimate the global minimum variance path for computing the free energy insertion into or deletion of small molecules from a dense fluid. We perform this optimization over all pair potentials, irrespective of functional form, using functional optimization with a two-body approximation for the radial distribution function. Surprisingly, the optimal pairwise path obtained via this method is almost identical to the path obtained using a optimized generalized "soft core" potential reported by Pham and Shirts [J. Chem. Phys. 135, 034114 (2011)]. We also derive the lowest variance non-pairwise potential path for molecular insertion or deletion and compare its efficiency to the pairwise path. Under certain conditions, non-pairwise pathways can reduce the total variance by up to 60% compared to optimal pairwise pathways. However, optimal non-pairwise pathways do not appear generally feasible for practical free energy calculations because an accurate estimate of the free energy, the parameter that is itself is desired, is required for constructing this non-pairwise path. Additionally, simulations at most intermediate states of these non-pairwise paths have significantly longer correlation times, often exceeding standard simulation lengths for solvation of bulky molecules. The findings suggest that the previously obtained soft core pathway is the lowest variance pathway for molecular insertion or deletion in practice. The findings also demonstrate the utility of functional optimization for determining the efficiency of thermodynamic processes performed with molecular simulation. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3697833]