Exploring Protein-Peptide Recognition Pathways Using a Supervised Molecular Dynamics Approach

Peptides have gained increased interest as therapeutic agents during recent years. The high specificity and relatively low toxicity of peptide drugs derive from their extremely tight binding to their targets. Indeed, understanding the molecular mechanism of protein-peptide recognition has important implications in the fields of biology, medicine, and pharmaceutical sciences. Even if crystallography and nuclear magnetic resonance are offering valuable atomic insights into the assembling of the protein-peptide complexes, the mechanism of their recognition and binding events remains largely unclear. In this work we report, for the first time, the use of a supervised molecular dynamics approach to explore the possible protein-peptide binding pathways within a timescale reduced up to three orders of magnitude compared with classical molecular dynamics. The better and faster understating of the protein-peptide recognition pathways could be very beneficial in enlarging the applicability of peptide-based drug design approaches in several biotechnological and pharmaceutical fields. [Display omitted] •Exploration of protein-peptide recognition pathways by molecular dynamics simulations•Direct depiction of protein-peptide recognition interaction networks•Observation of induced-fit phenomenon during peptides/peptidomimetics recognition•Alternative method for protein-peptide docking using molecular dynamics simulations Salmaso et al. report a novel computational strategy for the direct exploration of protein-peptide recognition pathways using a supervised molecular dynamics approach, named pepSuMD. This approach could have a relevant impact in various biotechnological and pharmaceutical applications where protein-peptide interaction plays a key role.