Treating entropy and conformational changes in implicit solvent Simulations of small molecules
Treating entropy and conformational changes in implicit solvent Simulations of small molecules
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DOI：
10.1021/jp0764384
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发表时间：
2008-01-24
影响因子：
3.3
通讯作者：
Chodera, John D.
中科院分区：
文献类型：
--
作者：
Mobley, David L.;Dill, Ken A.;Chodera, John D.
隐式溶剂模型在分子模拟和其他应用中越来越受欢迎，用于估计水溶液的溶剂化（水合）自由能。在许多情况下，这些模型的参数推导出重现小分子水合自由能的实验值。通常，这些水化自由能计算为一个单一的溶质构象，忽略溶剂化后的溶质构象变化。在这里，我们将这些影响使用炼金术的自由能方法。我们发现显着的错误时，水合自由能估计仅使用一个单一的溶质构象，即使是相对较小的，简单的，刚性溶质。例如，我们发现构象熵（T Δ S）的变化高达2.3千卡/摩尔后水合。有趣的是，构象熵的这些变化与可旋转键的数量相关性很差（R-2 = 0.03）。本研究表明，隐式溶剂模型可以通过消除溶质是刚性的近似来改进。
Implicit solvent models are increasingly popular for estimating aqueous solvation (hydration) free energies in molecular simulations and other applications. In many cases, parameters for these models are derived to reproduce experimental values for small molecule hydration free energies. Often, these hydration free energies are computed for a single solute conformation, neglecting solute conformational changes upon solvation. Here, we incorporate these effects using alchemical free energy methods. We find significant errors when hydration free energies are estimated using only a single solute conformation, even for relatively small, simple, rigid solutes. For example, we find conformational entropy (T Delta S) changes of up to 2.3 kcal/mol upon hydration. Interestingly, these changes in conformational entropy correlate poorly (R-2=0.03) with the number of rotatable bonds. The present study illustrates that implicit solvent modeling can be improved by eliminating the approximation that solutes are rigid.