Synchronous and Asynchronous Response in Dynamically Perturbed Proteins

Abstract

AbstractWe developed a Dynamic Gaussian Network Model to study perturbation and response in proteins. The model is based on the solution of the Langevin equation in the presence of noise and perturbation. A residue is perturbed periodically with a given frequency and the response of other residues is determined in terms of a storage and loss modulus of the protein. The amount of work lost upon periodic perturbation and the residues that contribute significantly to the lost work is determined. The model shows that perturbation introduces new dynamic correlations into the system with time delayed synchronous and asynchronous components. Residues whose perturbation induces large correlations in the protein and those that do not lead to correlations may be identified. The model is used to investigate the dynamic modulation of nanobodies. Despite its simplicity, the model explains several features of perturbation and response such as the role of loops and linkers in perturbation, dispersion of work of perturbation, and information transfer through preexisting pathways, all shown to be important factors in allostery.