Enhanced Sampling of Peptide Binding to Proteins through Gaussian Accelerated Molecular Dynamics Simulations

Abstract

Peptides mediate up to 40% of known protein-protein interactions in higher eukaryotes and play an important role in cellular signaling. However, it is challenging to sufficiently sample peptide-protein interactions through conventional molecular dynamics simulations, due to long timescales and extremely high system flexibility. Here, all-atom simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method have been applied for enhanced sampling of peptide binding to proteins. The GaMD simulations have identified important low-energy conformational states for three model peptide-protein complexes.