Integrating Protein Interaction Surface Prediction with a Fragment-Based Drug Design: Automatic Design of New Leads with Fragments on Energy Surfaces.

ABSTRACT: Protein-protein interactions (PPIs) have emerged in the past years as significant pharmacological targets in the development of new therapeutics due to their key roles in determining pathological pathways. Herein, we present fragments on energy surfaces, a simple and general design strategy that integrates the analysis of the dynamic and energetic signatures of proteins to unveil the substructures involved in PPIs, with docking, selection, and combination of drug-like fragments to generate new PPI inhibitor candidates. Specifically, structural representatives of the target protein are used as inputs for the blind physics-based prediction of potential protein interaction surfaces using the matrix of low coupling energy decomposition method. The predicted interaction surfaces are subdivided

SUBMITTER: Torielli L 

PROVIDER: S-EPMC9832486 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature