Hydration Free Energies in the FreeSolv Database Calculated with Polarized Iterative Hirshfeld Charges.
Hydration Free Energies in the FreeSolv Database Calculated with Polarized Iterative Hirshfeld Charges.
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DOI：
10.1021/acs.jcim.8b00180
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发表时间：
2018-09-24
影响因子：
5.6
通讯作者：
Vöhringer-Martinez E
中科院分区：
文献类型：
--
作者：
Riquelme M;Lara A;Mobley DL;Verstraelen T;Matamala AR;Vöhringer-Martinez E
生物分子系统的计算机模拟通常使用力场，它是简单的基于原子的经验函数的组合来描述分子相互作用。尽管可极化力场给出了分子间相互作用的更详细描述，但几十年前发展起来的不可极化力场通常仍然是首选，因为它们降低了计算成本。静电相互作用在生物分子系统中起着重要作用，在生物分子系统中用原子点电荷来描述。在这项工作中，我们讨论了不同的原子电荷的性能，结合Gaff力场，在Free Solv数据库中再现了实验的水合自由能。原子电荷的计算采用Hirshfeld-I和最小基迭代斯托克霍尔德(MBIS)两种原子分子方法。为了考虑极化效应，用隐式溶剂模型计算了溶质的电子密度，并将极化溶质所需的能量添加到自由能循环中。用误差模型分析了计算的水合自由能，揭示了与特定官能团或化学元素有关的系统误差。AM1-BCC和MBIS原子电荷方法与实验数据符合得最好。后者包括溶剂极化，对于所研究的613个有机分子，其均方根误差为2.0kcal−1。含磷分子和含酰胺、酯、胺官能团的分子偏离最大。
Computer simulations of bio-molecular systems often use force fields, which are combinations of simple empirical atom-based functions to describe the molecular interactions. Even though polarizable force fields give a more detailed description of intermolecular interactions, nonpolarizable force fields, developed several decades ago, are often still preferred because of their reduced computation cost. Electrostatic interactions play a major role in bio-molecular systems and are therein described by atomic point charges. In this work, we address the performance of different atomic charges to reproduce experimental hydration free energies in the FreeSolv database in combination with the GAFF force field. Atomic charges were calculated by two atoms-in-molecules approaches, Hirshfeld-I and Minimal Basis Iterative Stockholder (MBIS). To account for polarization effects, the charges were derived from the solute’s electron density computed with an implicit solvent model and the energy required to polarize the solute was added to the free energy cycle. The calculated hydration free energies were analyzed with an error model, revealing systematic errors associated with specific functional groups or chemical elements. The best agreement with the experimental data is observed for the AM1-BCC and the MBIS atomic charge methods. The latter includes the solvent polarization and present a root mean square error of 2.0 kcal mol−1 for the 613 organic molecules studied. The largest deviation was observed for phosphorus-containing molecules and the molecules with amide, ester and amine functional groups.
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影响因子：
2.8
作者：
BEUTLER, TC;MARK, AE;VANGUNSTEREN, WF
通讯作者：
VANGUNSTEREN, WF
影响因子：
4.4
作者：
Ayers, PW
通讯作者：
Ayers, PW
影响因子：
5.5
作者：
Gould, Tim;Bucko, Tomas
通讯作者：
Bucko, Tomas
影响因子：
4.4
作者：
BECKE, AD
通讯作者：
BECKE, AD
影响因子：
4.4
作者：
ESSMANN, U;PERERA, L;PEDERSEN, LG
通讯作者：
PEDERSEN, LG