Development and Benchmarking of Open Force Field 2.0.0: The Sage Small Molecule Force Field.
Development and Benchmarking of Open Force Field 2.0.0: The Sage Small Molecule Force Field.
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Open Force Field 2.0.0 的开发和基准测试：Sage 小分子力场。
DOI：
10.1021/acs.jctc.3c00039
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发表时间：
2023-06-13
影响因子：
5.5
通讯作者：
Mobley, David L.
中科院分区：
文献类型：
--
作者：
Boothroyd, Simon;Behara, Pavan Kumar;Madin, Owen C.;Hahn, David F.;Jang, Hyesu;Gapsys, Vytautas;Wagner, Jeffrey R.;Horton, Joshua T.;Dotson, David L.;Thompson, Matthew W.;Maat, Jessica;Gokey, Trevor;Wang, Lee-Ping;Cole, Daniel J.;Gilson, Michael K.;Chodera, John D.;Bayly, Christopher I.;Shirts, Michael R.;Mobley, David L.
我们引入了开放力场（OpenFF）2.0.0小分子力场，用于药物样分子，代号为Sage，它建立在我们之前的迭代Parsley基础上。OpenFF力场基于直接化学感知，其基于子结构查询容易地推广到高度多样化的化学集合。与之前的OpenFF迭代一样，Sage生成的OpenFF力场在蛋白质-配体模拟中得到验证，与AMBER生物聚合物力场兼容。在这项工作中，我们详细介绍了用于开发这个力场的方法，以及自Parsley 1.0.0发布以来所引入的创新和改进。Sage的一个特别重要的特征是一组针对凝聚相混合物数据重新训练的改进的Lennard-Jones（LJ）参数，这是OpenFF小分子力场线中LJ参数的第一次重新拟合。Sage还包含了比以前版本更大的量子化学计算数据库的价参数重新拟合，以及如何进行这种拟合的改进。力场基准显示了针对量子化学参考数据的一般性能指标的改进，例如优化的构象几何形状的均方根偏差（RMSD）、扭转指纹偏差（TFD）和改进的相对构象能量学（ΔΔE）。我们提出了各种基准，这些指标对我们以前的力场，以及在某些情况下，其他小分子力场。Sage还展示了在估计物理性质方面的改进性能，包括与各种热力学数据库中小分子性质的实验数据进行比较，如ΔHmix，ρ（x），ΔGsolv和Δ Gtranss。此外，我们以蛋白质-配体结合自由能（ΔGbind）为基准，其中Sage产生的结果在统计学上与以前的力场相似。所有的数据都是公开的，沿着关于如何重现训练结果的完整细节。
We introduce the Open Force Field (OpenFF) 2.0.0 small molecule force field for drug-like molecules, code-named Sage, which builds upon our previous iteration, Parsley. OpenFF force fields are based on direct chemical perception, which generalizes easily to highly diverse sets of chemistries based on substructure queries. Like the previous OpenFF iterations, the Sage generation of OpenFF force fields was validated in protein–ligand simulations to be compatible with AMBER biopolymer force fields. In this work, we detail the methodology used to develop this force field, as well as the innovations and improvements introduced since the release of Parsley 1.0.0. One particularly significant feature of Sage is a set of improved Lennard-Jones (LJ) parameters retrained against condensed phase mixture data, the first refit of LJ parameters in the OpenFF small molecule force field line. Sage also includes valence parameters refit to a larger database of quantum chemical calculations than previous versions, as well as improvements in how this fitting is performed. Force field benchmarks show improvements in general metrics of performance against quantum chemistry reference data such as root-mean-square deviations (RMSD) of optimized conformer geometries, torsion fingerprint deviations (TFD), and improved relative conformer energetics (ΔΔE). We present a variety of benchmarks for these metrics against our previous force fields as well as in some cases other small molecule force fields. Sage also demonstrates improved performance in estimating physical properties, including comparison against experimental data from various thermodynamic databases for small molecule properties such as ΔHmix, ρ(x), ΔGsolv, and ΔGtrans. Additionally, we benchmarked against protein–ligand binding free energies (ΔGbind), where Sage yields results statistically similar to previous force fields. All the data is made publicly available along with complete details on how to reproduce the training results at .
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影响因子：
1.6
作者：
Chodera, John D.;Swope, William C.;Dill, Ken A.
通讯作者：
Dill, Ken A.
影响因子：
4.4
作者：
BECKE, AD
通讯作者：
BECKE, AD
影响因子：
8.4
作者：
Gapsys V;Pérez-Benito L;Aldeghi M;Seeliger D;van Vlijmen H;Tresadern G;de Groot BL
通讯作者：
de Groot BL
影响因子：
4.3
作者：
Eastman P;Swails J;Chodera JD;McGibbon RT;Zhao Y;Beauchamp KA;Wang LP;Simmonett AC;Harrigan MP;Stern CD;Wiewiora RP;Brooks BR;Pande VS
通讯作者：
Pande VS
影响因子：
5.5
作者：
Boothroyd, Simon;Madin, Owen C.;Mobley, David L.;Wang, Lee-Ping;Chodera, John D.;Shirts, Michael R.
通讯作者：
Shirts, Michael R.