Petrov Drazen, Perthold Jan Walther, Oostenbrink Chris, de Groot Bert L, Gapsys Vytautas
Institute for Molecular Modeling and Simulation, Department of Material Sciences and Process Engineering, University of Natural Resources and Life Sciences, Vienna, Vienna 1190, Austria.
Christian Doppler Laboratory for Molecular Informatics in the Biosciences, University of Natural Resources and Life Sciences, Vienna, Vienna 1190, Austria.
J Chem Theory Comput. 2024 Jan 23;20(2):914-925. doi: 10.1021/acs.jctc.3c00757. Epub 2024 Jan 2.
The Coulomb interactions in molecular simulations are inherently approximated due to the finite size of the molecular box sizes amenable to current-day compute power. Several methods exist for treating long-range electrostatic interactions, yet these approaches are subject to various finite-size-related artifacts. Lattice-sum methods are frequently used to approximate long-range interactions; however, these approaches also suffer from artifacts which become particularly pronounced for free-energy calculations that involve charge changes. The artifacts, however, also affect the sampling when plain simulations are performed, leading to a biased ensemble. Here, we investigate two previously described model systems to determine if artifacts continue to play a role when overall neutral boxes are considered, in the context of both free-energy calculations and sampling. We find that ensuring that no net-charge changes take place, while maintaining a neutral simulation box, may be sufficient provided that the simulation boxes are large enough. Addition of salt to the solution (when appropriate) can further alleviate the remaining artifacts in the sampling or the calculated free-energy differences. We provide practical guidelines to avoid finite-size artifacts.
由于当前计算能力所适用的分子盒尺寸有限，分子模拟中的库仑相互作用本质上是近似的。存在几种处理长程静电相互作用的方法，但这些方法会受到各种与有限尺寸相关的假象影响。晶格和方法经常用于近似长程相互作用；然而，这些方法也存在假象，在涉及电荷变化的自由能计算中尤为明显。然而，这些假象在进行普通模拟时也会影响采样，导致系综有偏差。在这里，我们研究两个先前描述的模型系统，以确定在自由能计算和采样的背景下，当考虑整体中性盒时，假象是否继续起作用。我们发现，只要模拟盒足够大，在保持模拟盒中性的同时确保没有净电荷变化可能就足够了。在溶液中添加盐（在适当的时候）可以进一步减轻采样中剩余的假象或计算出的自由能差异。我们提供了避免有限尺寸假象的实用指南。
