Free Energy-Based Computational Methods for the Study of Protein-Peptide Binding Equilibria.

Abstract

This chapter discusses the theory and application of physics-based free energy methods to estimate protein-peptide binding free energies. It presents a statistical mechanics formulation of molecular binding, which is then specialized in three methodologies: (1) alchemical absolute binding free energy estimation with implicit solvation, (2) alchemical relative binding free energy estimation with explicit solvation, and (3) potential of mean force binding free energy estimation. Case studies of protein-peptide binding application taken from the recent literature are discussed for each method.