Long-range correlation in protein dynamics: Confirmation by structural data and normal mode analysis.

Proteins in cellular environments are highly susceptible. Local perturbations to any residue can be sensed by other spatially distal residues in the protein molecule, showing long-range correlations in the native dynamics of proteins. The long-range correlations of proteins contribute to many biological processes such as allostery, catalysis, and transportation. Revealing the structural origin of such long-range correlations is of great significance in understanding the design principle of biologically functional proteins. In this work, based on a large set of globular proteins determined by X-ray crystallography, by conducting normal mode analysis with the elastic network models, we demonstrate that such long-range correlations are encoded in the native topology of the proteins. To understand how native topology defines the structure and the dynamics of the proteins, we conduct scaling analysis on the size dependence of the slowest vibration mode, average path length, and modularity. Our results quantitatively describe how native proteins balance between order and disorder, showing both dense packing and fractal topology. It is suggested that the balance between stability and flexibility acts as an evolutionary constraint for proteins at different sizes. Overall, our result not only gives a new perspective bridging the protein structure and its dynamics but also reveals a universal principle in the evolution of proteins at all different sizes. Author summary: The long-range correlated fluctuations are closely related to many biological processes of the proteins, such as catalysis, ligand binding, biomolecular recognition, and transportation. In this paper, we elucidate the structural origin of the long-range correlation and describe how native contact topology defines the slow-mode dynamics of the native proteins. Our result suggests an evolutionary constraint for proteins at different sizes, which may shed light on solving many biophysical problems such as structure prediction, multi-scale molecular simulations, and the design of molecular machines. Moreover, in statistical physics, as the long-range correlations are notable signs of the critical point, unveiling the origin of such criticality can extend our understanding of the organizing principle of a large variety of complex systems. [ABSTRACT FROM AUTHOR]