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Shape-conditioned 3D Molecule Generation via Equivariant Diffusion Models

2023-08-23 · Ziqi Chen, Bo Peng, Srinivasan Parthasarathy, Xia Ning

Ligand-based drug design aims to identify novel drug candidates of similar shapes with known active molecules. In this paper, we formulated an in silico shape-conditioned molecule generation problem to generate 3D molecule structures conditioned on the shape of a given molecule. To address this problem, we developed a translation- and rotation-equivariant shape-guided generative model ShapeMol. ShapeMol consists of an equivariant shape encoder that maps molecular surface shapes into latent embeddings, and an equivariant diffusion model that generates 3D molecules based on these embeddings. Experimental results show that ShapeMol can generate novel, diverse, drug-like molecules that retain 3D molecular shapes similar to the given shape condition. These results demonstrate the potential of ShapeMol in designing drug candidates of desired 3D shapes binding to protein target pockets.

📄 PDF Abstract BibTeX arXiv:2308.11890

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3D Molecule GenerationDrug Design

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Diffusion Diffusion models generate samples by gradually removing noise from a signal, and their training objective can be expressed as a reweighted variational lower-bound…

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