Electrostatic embedding in large-scale first principles quantum mechanical calculations on biomolecules
Electrostatic embedding in large-scale first principles quantum mechanical calculations on biomolecules
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DOI：
10.1063/1.3665893
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发表时间：
2011-12-14
影响因子：
4.4
通讯作者：
Skylaris, Chris-Kriton
中科院分区：
文献类型：
--
作者：
Fox, Stephen J.;Pittock, Chris;Skylaris, Chris-Kriton
通常需要具有原子细节的生物分子模拟来描述具有化学精度的相互作用，例如计算酶中的结合自由能或化学反应。力场通常用于此任务，但这些依赖于广泛的参数化，在某些情况下可能导致有限的准确性和可转移性，例如具有不寻常官能团的配体。这些限制可以通过密度泛函理论（DFT）等方法的第一性原理计算来克服，但计算成本要高得多。静电嵌入的使用可以通过在高度局部化的电荷分布方面表示模拟系统的一部分来显着降低这种成本。这些经典的电荷分布是与量子系统静电耦合的，代表了量子系统所处环境的影响。本文描述并评价了这样一种在密度计算过程中由嵌入电荷引起的电子密度极化自一致的嵌入方案。我们已经在线性缩放DFT程序中实现了该方案，因为我们的目标是用DFT处理整个生物分子（如蛋白质）和大部分溶剂。我们在计算配体与生物分子和溶剂的相互作用能时测试了这种方法，并研究了在什么条件下，这些方法可以与用DFT描述整个系统时的精度相同，适用于各种中性和带电物质。(C) 2011年美国物理研究所。(doi: 10.1063/1.3665893)
Biomolecular simulations with atomistic detail are often required to describe interactions with chemical accuracy for applications such as the calculation of free energies of binding or chemical reactions in enzymes. Force fields are typically used for this task but these rely on extensive parameterisation which in cases can lead to limited accuracy and transferability, for example for ligands with unusual functional groups. These limitations can be overcome with first principles calculations with methods such as density functional theory (DFT) but at a much higher computational cost. The use of electrostatic embedding can significantly reduce this cost by representing a portion of the simulated system in terms of highly localised charge distributions. These classical charge distributions are electrostatically coupled with the quantum system and represent the effect of the environment in which the quantum system is embedded. In this paper we describe and evaluate such an embedding scheme in which the polarisation of the electronic density by the embedding charges occurs self-consistently during the calculation of the density. We have implemented this scheme in a linear-scaling DFT program as our aim is to treat with DFT entire biomolecules (such as proteins) and large portions of the solvent. We test this approach in the calculation of interaction energies of ligands with biomolecules and solvent and investigate under what conditions these can be obtained with the same level of accuracy as when the entire system is described by DFT, for a variety of neutral and charged species. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3665893]