Force fields form the basis for classical molecular simulations, and their accuracy is crucial for the quality of, for instance, protein–ligand binding simulations in drug discovery. The huge diversity of small-molecule chemistry makes it a challenge to build and parameterize a suitable force field. The Open Force Field Initiative is a combined industry and academic consortium developing a state-of-the-art small-molecule force field. In this report, industry members of the consortium worked together to objectively evaluate the performance of the force fields (referred to here as OpenFF) produced by the initiative on a combined public and proprietary dataset of 19,653 relevant molecules selected from their internal research and compound collections. This evaluation was important because it was completely blind; at most partners, none of the molecules or data were used in force field development or testing prior to this work. We compare the Open Force Field “Sage” version 2.0.0 and “Parsley” version 1.3.0 with GAFF-2.11-AM1BCC, OPLS4, and SMIRNOFF99Frosst. We analyzed force-field-optimized geometries and conformer energies compared to reference quantum mechanical data. We show that OPLS4 performs best, and the latest Open Force Field release shows a clear improvement compared to its predecessors. The performance of established force fields such as GAFF-2.11 was generally worse. While OpenFF researchers were involved in building the benchmarking infrastructure used in this work, benchmarking was done entirely in-house within industrial organizations and the resulting assessment is reported here. This work assesses the force field performance using separate benchmarking steps, external datasets, and involving external research groups. This effort may also be unique in terms of the number of different industrial partners involved, with 10 different companies participating in the benchmark efforts.

中文翻译：

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从开放力场协同评估分子几何形状和能量

力场构成了经典分子模拟的基础，其准确性对于药物发现中的蛋白质-配体结合模拟等质量至关重要。小分子化学的巨大多样性使得构建和参数化合适的力场成为一项挑战。Open Force Field Initiative 是一个联合行业和学术联盟，致力于开发最先进的小分子力场。在这份报告中，该联盟的行业成员共同合作客观地评估了该倡议产生的力场（此处称为 OpenFF）的性能，该数据集包含从其内部研究和化合物集合中选出的 19,653 种相关分子的公共和专有数据集. 这种评估很重要，因为它完全是盲目的；在大多数合作伙伴中，在这项工作之前，没有任何分子或数据被用于力场开发或测试。我们将 Open Force Field“Sage”2.0.0 版和“Parsley”1.3.0 版与 GAFF-2.11-AM1BCC、OPLS4 和 SMIRNOFF99Frosst 进行比较。与参考量子力学数据相比，我们分析了力场优化的几何形状和构象能量。我们表明 OPLS4 表现最好，最新的 Open Force Field 版本与其前身相比有明显的改进。GAFF-2.11 等已建立的力场的性能普遍较差。虽然 OpenFF 研究人员参与构建了这项工作中使用的基准测试基础设施，但基准测试完全是在工业组织内部完成的，因此在此报告了评估结果。这项工作使用单独的基准测试步骤、外部数据集并涉及外部研究小组来评估力场性能。就所涉及的不同行业合作伙伴的数量而言，这项工作也可能是独一无二的，有 10 家不同的公司参与了基准测试工作。