Equivariant 3D-conditional diffusion model for molecular linker design

Abstract Fragment-based drug discovery has been an effective paradigm in early-stage drug development. An open challenge in this area is designing linkers between disconnected molecular fragments of interest to obtain chemically relevant candidate drug molecules. In this work, we propose DiffLinker, an E(3)-equivariant three-dimensional conditional diffusion model for molecular linker design. Given a set of disconnected fragments, our model places missing atoms in between and designs a molecule incorporating all the initial fragments. Unlike previous approaches that are only able to connect pairs of molecular fragments, our method can link an arbitrary number of fragments. Additionally, the model automatically…

• EC
  European Commission

  Award: 945363
• ÉP
  École Polytechnique Fédérale de Lausanne
• EA
  Engineering and Physical Sciences Research Council