Nanoscience Center and Department of Chemistry, University of Jyväskylä, 40014Jyväskylä, Finland.
Department of Applied Physics and Swedish e-Science Research Center, Science for Life Laboratory, KTH Royal Institute of Technology, 100 44Stockholm, Sweden.
J Chem Theory Comput. 2022 Oct 11;18(10):6148-6160. doi: 10.1021/acs.jctc.2c00516. Epub 2022 Sep 21.
Molecular dynamics (MD) computer simulations are used routinely to compute atomistic trajectories of complex systems. Systems are simulated in various ensembles, depending on the experimental conditions one aims to mimic. While constant energy, temperature, volume, and pressure are rather straightforward to model, pH, which is an equally important parameter in experiments, is more difficult to account for in simulations. Although a constant pH algorithm based on the λ-dynamics approach by Brooks and co-workers [Kong, X.; Brooks III, C. L. , , 2414-2423] was implemented in a fork of the GROMACS molecular dynamics program, uptake has been rather limited, presumably due to the poor scaling of that code with respect to the number of titratable sites. To overcome this limitation, we implemented an alternative scheme for interpolating the Hamiltonians of the protonation states that makes the constant pH molecular dynamics simulations almost as fast as a normal MD simulation with GROMACS. In addition, we implemented a simpler scheme, called multisite representation, for modeling side chains with multiple titratable sites, such as imidazole rings. This scheme, which is based on constraining the sum of the λ-coordinates, not only reduces the complexity associated with parametrizing the intramolecular interactions between the sites but also is easily extendable to other molecules with multiple titratable sites. With the combination of a more efficient interpolation scheme and multisite representation of titratable groups, we anticipate a rapid uptake of constant pH molecular dynamics simulations within the GROMACS user community.
分子动力学（MD）计算机模拟通常用于计算复杂系统的原子轨迹。根据旨在模拟的实验条件，系统在各种系综中进行模拟。虽然恒能、恒温和恒压模型相对简单，但在模拟中更难处理 pH 值，因为 pH 值是实验中同样重要的参数。尽管 Brooks 及其同事的基于 λ 动力学方法的恒 pH 值算法 [Kong, X.; Brooks III, C. L.,, 2414-2423] 已在 GROMACS 分子动力学程序的一个分支中实现，但采用率相当有限，大概是由于该代码与可滴定位点的数量的比例较差。为了克服这一限制，我们实现了一种替代方案，用于内插质子化状态的哈密顿量，使恒 pH 值分子动力学模拟的速度几乎与 GROMACS 进行的正常 MD 模拟一样快。此外，我们实现了一种更简单的方案，称为多位点表示，用于模拟具有多个可滴定位点的侧链，例如咪唑环。该方案基于约束 λ 坐标的总和，不仅减少了参数化位点之间的分子内相互作用的复杂性，而且易于扩展到具有多个可滴定位点的其他分子。通过更有效的内插方案和可滴定基团的多站点表示的组合，我们预计恒 pH 值分子动力学模拟在 GROMACS 用户社区中的采用率将会迅速提高。
