Alchemical prediction of hydration free energies for SAMPL.
Alchemical prediction of hydration free energies for SAMPL.
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DOI：
10.1007/s10822-011-9528-8
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发表时间：
2012-05
影响因子：
3.5
通讯作者：
Rice, Julia E.
中科院分区：
文献类型：
--
作者：
Mobley, David L.;Liu, Shaui;Cerutti, David S.;Swope, William C.;Rice, Julia E.
水化自由能的计算已成为力场的重要检验。基于分子动力学模拟的炼金术自由能计算提供了一种严格的方法来计算特定力场的自由能，只要有足够的采样。在这里，我们报告了一组小分子的炼金术水合自由能计算结果，这些小分子包括2011年蛋白质和配体建模统计评估（SAMPL）挑战。我们的计算在很大程度上基于具有几种不同电荷模型的广义琥珀力场（GAFF），并且根据电荷模型，我们在1.4-2.2 kcal/mol范围内实现了RMS误差，略高于我们在以前的研究中通常观察到的误差。测试装置包括乙烷、联苯和二苄基二恶英，以及每种物质的一系列氯化衍生物。我们发现，对于这个集合，使用来自MP2/cc-PVTZ SCRF RESP拟合的高质量部分电荷与使用AM 1-BCC部分电荷的实验的一致性略有改善，因为我们更通常这样做，与我们最近的发现保持一致。切换到具有AM 1-BCC电荷的OPLS Lennard-Jones参数也改善了与实验的一致性。我们还发现了每个分子系列中的一些化学趋势，我们可以解释，但也有一些惊喜，包括一些计算捕获的和一些没有捕获的。
Hydration free energy calculations have become important tests of force fields. Alchemical free energy calculations based on molecular dynamics simulations provide a rigorous way to calculate these free energies for a particular force field, given sufficient sampling. Here, we report results of alchemical hydration free energy calculations for the set of small molecules comprising the 2011 Statistical Assessment of Modeling of Proteins and Ligands (SAMPL) challenge. Our calculations are largely based on the Generalized Amber Force Field (GAFF) with several different charge models, and we achieved RMS errors in the 1.4-2.2 kcal/mol range depending on charge model, marginally higher than what we typically observed in previous studies. The test set consists of ethane, biphenyl, and a dibenzyl dioxin, as well as a series of chlorinated derivatives of each. We found that, for this set, using high-quality partial charges from MP2/cc-PVTZ SCRF RESP fits provided marginally improved agreement with experiment over using AM1-BCC partial charges as we have more typically done, in keeping with our recent findings. Switching to OPLS Lennard-Jones parameters with AM1-BCC charges also improves agreement with experiment. We also find a number of chemical trends within each molecular series which we can explain, but there are also some surprises, including some that are captured by the calculations and some that are not.
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影响因子：
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