Analysis of Software Methods for Estimation of Protein-Protein Relative Binding Affinity

Abstract

Analysis of Software Methods for Estimation of Protein-Protein Relative Binding Affinity: Biophysical modeling of protein-protein interactions provides insight into how and why proteins behave in specific ways and is useful for estimating how amino acid mutations modify protein-protein binding affinity, a topic with significant clinical applications. Binding affinity prediction software vary in the complexity of information used to create predictions. Our hypothesis is that software methods using a wider variety of information will provide more accurate binding affinity predictions than those relying on a single descriptive energy function. We compare six methods that range from empirical to semi-empirical. We generated estimates for sixteen protein complex test systems with experimental data. A performance score for each program was determined based on correlation to experimental data and the ability to correctly estimate the sign of the relative binding affinity.