Effects of ligand binding upon flexibility of proteins

TL;DR

This paper introduces a new equation to map protein stiffness changes upon ligand binding, using molecular dynamics and Gaussian Network Model, demonstrated through dimerization of AKT1.

Contribution

A novel model linking fluctuation correlations to protein stiffness changes, enhancing understanding of ligand-induced flexibility alterations.

Findings

Stiffness maps reveal regions of increased or decreased flexibility upon ligand binding.

The model accurately predicts stiffness changes in AKT1 dimerization.

Correlation-based approach improves insights into protein dynamics.

Abstract

Binding of a ligand on a protein changes the flexibility of certain parts of the protein, which directly affects its function. These changes are not the same at each point, some parts become more flexible and some others become stiffer. Here, an equation is derived that gives the stiffness map for proteins. The model is based on correlations of fluctuations of pairs of points that need to be evaluated by molecular dynamics simulations. The model is also cast in terms of the Gaussian Network Model and changes of stiffness upon dimerization of AKT1 are evaluated as an example.