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Diffusion Models in $\textit{De Novo}$ Drug Design

2024-06-07 · Amira Alakhdar, Barnabas Poczos, Newell Washburn

Diffusion models have emerged as powerful tools for molecular generation, particularly in the context of 3D molecular structures. Inspired by non-equilibrium statistical physics, these models can generate 3D molecular structures with specific properties or requirements crucial to drug discovery. Diffusion models were particularly successful at learning 3D molecular geometries' complex probability distributions and their corresponding chemical and physical properties through forward and reverse diffusion processes. This review focuses on the technical implementation of diffusion models tailored for 3D molecular generation. It compares the performance, evaluation methods, and implementation details of various diffusion models used for molecular generation tasks. We cover strategies for atom and bond representation, architectures of reverse diffusion denoising networks, and challenges associated with generating stable 3D molecular structures. This review also explores the applications of diffusion models in $\textit{de novo}$ drug design and related areas of computational chemistry, such as structure-based drug design, including target-specific molecular generation, molecular docking, and molecular dynamics of protein-ligand complexes. We also cover conditional generation on physical properties, conformation generation, and fragment-based drug design. By summarizing the state-of-the-art diffusion models for 3D molecular generation, this review sheds light on their role in advancing drug discovery as well as their current limitations.

📄 PDF Abstract BibTeX arXiv:2406.08511

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Computational chemistryDenoisingDrug DesignDrug DiscoveryMolecular Docking

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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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