Predicting hydration free energies with a hybrid QM/MM approach: an evaluation of implicit and explicit solvation models in SAMPL4.
Predicting hydration free energies with a hybrid QM/MM approach: an evaluation of implicit and explicit solvation models in SAMPL4.
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使用混合 QM/MM 方法预测水合自由能：SAMPL4 中隐式和显式溶剂化模型的评估
DOI：
10.1007/s10822-014-9708-4
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发表时间：
2014-03
影响因子：
3.5
通讯作者：
Brooks, Bernard R.
中科院分区：
文献类型：
--
作者：
Koenig, Gerhard;Pickard, Frank C.;Mei, Ye;Brooks, Bernard R.
正确描述溶质-水相互作用对于准确模拟大多数生物现象是至关重要的。有几种高精度的量子方法可以通过使用隐式和显式溶剂来处理溶剂化。然而，到目前为止，对这些方法的大多数评价都是基于单一构象，这忽略了溶质熵。在这里，我们提出了一种确定水合自由能的新方法的首次测试，该方法使用分子力学(MM)来采样相空间，并使用量子力学(QM)来评估势能。自由能是用非玻耳兹曼-贝内特(NBB)方法重新加权得到的。在此上下文中，该方法被称为QM-NBB。基于MM样品的快照并考虑其正确的玻尔兹曼权重，有可能获得包含溶质熵影响的水化自由能。我们评估了几种QM隐式溶剂模型的性能，以及SAMPL4水合自由能挑战的盲子集显式溶剂QM/MM的性能。经典的分子动力学自由能模拟得到的均方根偏差(RMSD)分别为2.8和2.3千卡/摩尔，而混合方法的均方根偏差(RMSD)改进后为1.6千卡/摩尔。通过选择合适的官能团和基组，RMSD可以降低到1千卡/摩尔，用于基于单一构象的计算。对一组具有挑战性的分子的结果表明，通过使用NBB与SMD隐式溶剂模型重新加权MM轨迹，可以进一步降低RMSD。
The correct representation of solute-water interactions is essential for the accurate simulation of most biological phenomena. Several highly accurate quantum methods are available to deal with solvation by using both implicit and explicit solvents. So far, however, most evaluations of those methods were based on a single conformation, which neglects solute entropy. Here, we present the first test of a novel approach to determine hydration free energies that uses molecular mechanics (MM) to sample phase space and quantum mechanics (QM) to evaluate the potential energies. Free energies are determined by using re-weighting with the Non-Boltzmann Bennett (NBB) method. In this context, the method is referred to as QM-NBB. Based on snapshots from MM sampling and accounting for their correct Boltzmann weight, it is possible to obtain hydration free energies that incorporate the effect of solute entropy. We evaluate the performance of several QM implicit solvent models, as well as explicit solvent QM/MM for the blind subset of the SAMPL4 hydration free energy challenge. While classical free energy simulations with molecular dynamics give root mean square deviations (RMSD) of 2.8 and 2.3 kcal/mol, the hybrid approach yields an improved RMSD of 1.6 kcal/mol. By selecting an appropriate functional and basis set, the RMSD can be reduced to 1 kcal/mol for calculations based on a single conformation. Results for a selected set of challenging molecules imply that this RMSD can be further reduced by using NBB to reweight MM trajectories with the SMD implicit solvent model.
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影响因子：
4.1
作者：
BENNETT, CH
通讯作者：
BENNETT, CH
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作者：
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