Fine-tuning molecular mechanics force fields to experimental free energy measurements.

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Tác giả: John D Chodera, Joshua Fass, Dominic Rufa

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : bioRxiv : the preprint server for biology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 217389

Alchemical free energy methods using molecular mechanics (MM) force fields are essential tools for predicting thermodynamic properties of small molecules, especially via free energy calculations that can estimate quantities relevant for drug discovery such as affinities, selectivities, the impact of target mutations, and ADMET properties. While traditional MM forcefields rely on hand-crafted, discrete atom types and parameters, modern approaches based on graph neural networks (GNNs) learn continuous embedding vectors that represent chemical environments from which MM parameters can be generated. Excitingly, GNN parameterization approaches provide a fully end-to-end differentiable model that offers the possibility of systematically improving these models using experimental data. In this study, we treat a pretrained GNN force field-here, espaloma-0.3.2-as a
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