New computational protein design methods for de novo small molecule binding sites.

ABSTRACT: Protein binding to small molecules is fundamental to many biological processes, yet it remains challenging to predictively design this functionality de novo. Current state-of-the-art computational design methods typically rely on existing small molecule binding sites or protein scaffolds with existing shape complementarity for a target ligand. Here we introduce new methods that utilize pools of discrete contacts between protein side chains and defined small molecule ligand substructures (ligand fragments) observed in the Protein Data Bank. We use the Rosetta Molecular Modeling Suite to recombine protein side chains in these contact pools to generate hundreds of thousands of energetically favorable binding sites for a target ligand. These composite binding sites are built into existing scaf

SUBMITTER: Lucas JE 

PROVIDER: S-EPMC7575090 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature