PILOT: equivariant diffusion for pocket-conditioned de novo ligand generation with multi-objective guidance via importance sampling.

ABSTRACT: The generation of ligands that both are tailored to a given protein pocket and exhibit a range of desired chemical properties is a major challenge in structure-based drug design. Here, we propose an in silico approach for the de novo generation of 3D ligand structures using the equivariant diffusion model PILOT, combining pocket conditioning with a large-scale pre-training and property guidance. Its multi-objective trajectory-based importance sampling strategy is designed to direct the model towards molecules that not only exhibit desired characteristics such as increased binding affinity for a given protein pocket but also maintains high synthetic accessibility. This ensures the practicality of sampled molecules, thus maximizing their potential for the drug discovery pipelin

SUBMITTER: Cremer J 

PROVIDER: S-EPMC11348832 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature