Katzberger Paul, Pultar Felix, Riniker Sereina
Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 2, Zürich 8093, Switzerland.
J Chem Theory Comput. 2025 Aug 12;21(15):7450-7459. doi: 10.1021/acs.jctc.5c00728. Epub 2025 Jul 28.
The conformational ensemble of a molecule is strongly influenced by the surrounding environment. Correctly modeling the effect of any given environment is, hence, of pivotal importance in computational studies. Machine learning (ML) has been shown to be able to model these interactions probabilistically, with successful applications demonstrated for classical molecular dynamics. While first instances of ML implicit solvents for quantum-mechanical (QM) calculations exist, the high computational cost of QM reference calculations hinders the development of a generally applicable ML implicit solvent model for QM calculations. Here, we present a novel way of developing such a general machine-learned QM implicit solvent model by transferring knowledge obtained from classical interactions to QM, emulating a QM/MM setup with electrostatic embedding and a nonpolarizable MM solvent. This has the profound advantages that neither QM/MM reference calculations nor experimental data are required for training and that the obtained graph neural network (GNN)-based implicit solvent model (termed QM-GNNIS) is compatible with any functional and basis set. QM-GNNIS is currently applicable to small organic molecules and describes 39 different organic solvents. The performance of QM-GNNIS is validated on NMR and IR experiments, demonstrating that the approach can reproduce experimentally observed trends unattainable by state-of-the-art implicit-solvent models paired with static QM calculations.
分子的构象系综受到周围环境的强烈影响。因此,在计算研究中正确模拟任何给定环境的影响至关重要。机器学习(ML)已被证明能够以概率方式对这些相互作用进行建模,并且在经典分子动力学方面有成功的应用实例。虽然存在用于量子力学(QM)计算的ML隐式溶剂的首个实例,但QM参考计算的高计算成本阻碍了用于QM计算的通用ML隐式溶剂模型的开发。在此,我们提出了一种开发此类通用机器学习QM隐式溶剂模型的新方法,即通过将从经典相互作用中获得的知识转移到QM,模拟具有静电嵌入和不可极化MM溶剂的QM/MM设置。这具有深远的优势,即训练既不需要QM/MM参考计算也不需要实验数据,并且所获得的基于图神经网络(GNN)的隐式溶剂模型(称为QM-GNNIS)与任何泛函和基组兼容。QM-GNNIS目前适用于小分子有机化合物,并描述了39种不同的有机溶剂。QM-GNNIS的性能在核磁共振(NMR)和红外(IR)实验中得到验证,表明该方法能够重现当前最先进的隐式溶剂模型与静态QM计算所无法实现的实验观测趋势。