Papers › Physics-informed generative model for drug-like molecule conformers

Physics-informed generative model for drug-like molecule conformers

29 Feb 2024arXiv:2403.07925archive 2025-07-28

David C. Williams, Neil Inala

We present a diffusion-based, generative model for conformer generation. Our model is focused on the reproduction of bonded structure and is constructed from the associated terms traditionally found in classical force fields to ensure a physically relevant representation. Techniques in deep learning are used to infer atom typing and geometric parameters from a training set. Conformer sampling is achieved by taking advantage of recent advancements in diffusion-based generation. By training on large, synthetic data sets of diverse, drug-like molecules optimized with the semiempirical GFN2-xTB method, high accuracy is achieved for bonded parameters, exceeding that of conventional, knowledge-based methods. Results are also compared to experimental structures from the Protein Databank (PDB) and Cambridge Structural Database (CSD).

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