PDBcor: An Automated Correlation Extraction Calculator for Multi-State Protein Structures

Abstract

Allostery and correlated motion are key elements linking protein dynamics with mechanisms of action of proteins. Here we present PDBCor, an automated and unbiased method for the detection and analysis of correlated motions from experimental multi-state protein structures using torsion angle and distance statistics that does not require any structure superposition. Clustering of protein conformers allows us to extract correlations in the form of mutual information based on information theory. With PDBcor, we elucidated correlated motion in the WW domain of PIN1, the protein GB3, and the enzyme cyclophilin in line with reported findings. Correlations extracted with PDBcor can be utilized in subsequent assays including NMR multi-state structure optimization and validation. As a guide for the interpretation of PDBcor results, we provide a series of protein structure ensembles that exhibit different levels of correlation, including non-correlated, locally correlated, and globally correlated ensembles.