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开发与基准测试 Open Force Field 2.0.0:Sage 小分子力场

Development and Benchmarking of Open Force Field 2.0.0: The Sage Small Molecule Force Field.

机构信息

Boothroyd Scientific Consulting Ltd., London WC2H 9JQ, U.K.

Department of Pharmaceutical Sciences, University of California, Irvine, California 92697, United States.

出版信息

J Chem Theory Comput. 2023 Jun 13;19(11):3251-3275. doi: 10.1021/acs.jctc.3c00039. Epub 2023 May 11.


DOI:10.1021/acs.jctc.3c00039
PMID:37167319
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10269353/
Abstract

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 (ΔΔ). 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 Δ, ρ(), Δ, and Δ. Additionally, we benchmarked against protein-ligand binding free energies (Δ), 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 https://github.com/openforcefield/openff-sage.

摘要

我们引入了名为 Sage 的 Open Force Field (OpenFF) 2.0.0 小分子力场,用于药物样分子,它建立在我们之前的迭代 Parsley 之上。OpenFF 力场基于直接的化学感知,这种感知可以很容易地推广到基于子结构查询的高度多样化的化学物质。与之前的 OpenFF 迭代一样,Sage 生成的 OpenFF 力场在蛋白质-配体模拟中进行了验证,以与 AMBER 生物聚合物力场兼容。在这项工作中,我们详细介绍了开发该力场所使用的方法,以及自 Parsley 1.0.0 发布以来引入的创新和改进。Sage 的一个特别重要的特点是一组经过改进的 Lennard-Jones (LJ) 参数,这些参数是根据凝聚相混合物数据重新训练的,这是 OpenFF 小分子力场系列中首次重新拟合 LJ 参数。Sage 还包括根据比以前版本更大的量子化学计算数据库重新拟合的价参数,以及改进了拟合的方式。力场基准测试显示,在与量子化学参考数据(如优化构象几何 RMSD、扭转指纹偏差 (TFD) 和改进的相对构象能)的一般性能指标方面有了改进。我们针对这些指标展示了与我们之前的力场以及在某些情况下与其他小分子力场的各种基准测试。Sage 还在估计物理性质方面表现出了更好的性能,包括与各种小分子性质的热力学数据库的实验数据(如Δ、ρ()、Δ和Δ)进行比较。此外,我们还针对蛋白质-配体结合自由能 (Δ) 进行了基准测试,Sage 的结果在统计上与之前的力场相似。所有数据都在 https://github.com/openforcefield/openff-sage 上公开提供,并详细介绍了如何重现训练结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f99/10269353/37af84da9c8b/ct3c00039_0014.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f99/10269353/71f54b120d08/ct3c00039_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f99/10269353/b931d8d97ef6/ct3c00039_0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f99/10269353/37af84da9c8b/ct3c00039_0014.jpg

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本文引用的文献

[1]
Collaborative Assessment of Molecular Geometries and Energies from the Open Force Field.

J Chem Inf Model. 2022-12-12

[2]
Best practices for constructing, preparing, and evaluating protein-ligand binding affinity benchmarks [Article v0.1].

Living J Comput Mol Sci. 2022

[3]
Open Force Field BespokeFit: Automating Bespoke Torsion Parametrization at Scale.

J Chem Inf Model. 2022-11-28

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End-to-end differentiable construction of molecular mechanics force fields.

Chem Sci. 2022-9-8

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Preserving the Integrity of Empirical Force Fields.

J Chem Inf Model. 2022-8-22

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Exploration and validation of force field design protocols through QM-to-MM mapping.

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J Chem Theory Comput. 2022-6-14

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Towards improved FAIRness of the ThermoML Archive.

J Comput Chem. 2022-5-5

[10]
Pre-Exascale Computing of Protein-Ligand Binding Free Energies with Open Source Software for Drug Design.

J Chem Inf Model. 2022-3-14

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