Quantifying Disorder in a Protein by Mapping its Locally Correlated Structure and Kinetics

Abstract

Proteins under physiological conditions are inherently mobile and sample a vast array of structures. Consequently, the need arises, on the one hand, at a local level to determine the independent moving parts and their associated conformations and kinetics, and on the other hand, at a global level, to quantify the disorder in the full protein molecule. We present an approach that provides these quantities in the form of local kinetic network models, which are constructed by analyzing the molecular dynamics (MD) trajectories of the protein molecule. Entropies of independent parts of the molecule are quantified. The method outlined here, using the Trp-cage miniprotein prototype, offers a new tool to understand the dynamic structural changes that ultimately govern the functioning of a protein. The method is particularly suited to problems where there are subtle changes in the structure or dynamics at local levels, for example, due to ligand binding.