Implementation of the QUBE Force Field in SOMD for High-Throughput Alchemical Free-Energy Calculations.
Implementation of the QUBE Force Field in SOMD for High-Throughput Alchemical Free-Energy Calculations.
复制标题
在 SOMD 中实施 QUBE 力场以进行高通量炼金术自由能计算。
DOI：
10.1021/acs.jcim.1c00328
复制
发表时间：
2021
影响因子：
5.6
通讯作者：
Nelson L
中科院分区：
文献类型：
--
作者：
Nelson L
量子力学定制（QUBE）力场方法的开发是为了促进势能函数参数的自动推导，以模拟蛋白质-配体结合。迄今为止，该方法已在蛋白质-配体复合物的蒙特卡罗模拟中得到验证。我们在此描述 QUBE 力场在炼金术自由能计算分子动力学模拟软件包 SOMD 中的实现。通过展示使用 SOMD 和 GROMACS 软件包中的 QUBE 力场计算的绝对水合自由能的再现性，验证了该实现。我们通过涉及两个系列的 HIV-1 逆转录酶非核苷抑制剂的案例研究进一步证明，现代模拟包中 QUBE 的可用性可有效利用图形处理单元加速，将促进高通量炼金术自由能计算。
The quantum mechanical bespoke (QUBE) force-field approach has been developed to facilitate the automated derivation of potential energy function parameters for modeling protein–ligand binding. To date, the approach has been validated in the context of Monte Carlo simulations of protein–ligand complexes. We describe here the implementation of the QUBE force field in the alchemical free-energy calculation molecular dynamics simulation package SOMD. The implementation is validated by demonstrating the reproducibility of absolute hydration free energies computed with the QUBE force field across the SOMD and GROMACS software packages. We further demonstrate, by way of a case study involving two series of non-nucleoside inhibitors of HIV-1 reverse transcriptase, that the availability of QUBE in a modern simulation package that makes efficient use of graphics processing unit acceleration will facilitate high-throughput alchemical free-energy calculations.