School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom.
J Chem Phys. 2011 Dec 14;135(22):224107. 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.
生物分子模拟通常需要原子细节来描述具有化学精度的相互作用，例如计算结合自由能或酶中的化学反应。为此通常使用力场，但这些力场依赖于广泛的参数化，在某些情况下会导致有限的准确性和可转移性，例如对于具有不寻常官能团的配体。这些限制可以通过使用第一性原理计算方法（如密度泛函理论（DFT））来克服，但计算成本要高得多。静电嵌入可以通过用高度局部化的电荷分布来表示模拟系统的一部分来显著降低成本。这些经典电荷分布与量子系统静电耦合，代表了量子系统所处环境的影响。在本文中，我们描述并评估了这样一种嵌入方案，其中嵌入电荷对电子密度的极化在密度计算过程中是自洽的。我们已经在一个线性标度的 DFT 程序中实现了这个方案，因为我们的目标是用 DFT 来处理整个生物分子（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方面测试了这种方法，并研究了在什么条件下可以达到与整个系统用 DFT 描述相同的精度，对于各种中性和带电物种。
