Local transition gradients determine the global attributes of protein energy landscapes

TL;DR

This paper reveals how local atomic interactions in proteins influence their global energy landscapes, using molecular dynamics and network analysis to map the relationship between local fluctuations and global conformational changes.

Contribution

It introduces a novel approach combining transition gradients networks and minimum-spanning-tree analysis to map protein energy landscapes without prior knowledge of key degrees of freedom.

Findings

Fast peptide relaxations shape the global free-energy landscape

Transition gradients networks effectively connect local and global dynamics

The method provides high-resolution mapping of protein thermodynamics

Abstract

The dynamical characterization of proteins is crucial to understand protein function. From a microscopic point of view, protein dynamics is governed by the local atomic interactions that, in turn, trigger the functional conformational changes. Unfortunately, the relationship between local atomic fluctuations and global protein rearrangements is still elusive. Here, atomistic molecular dynamics simulations in conjunction with complex network analysis show that fast peptide relaxations effectively build the backbone of the global free-energy landscape, providing a connection between local and global atomic rearrangements. A minimum-spanning-tree representation, built on the base of transition gradients networks, results in a high resolution mapping of the system dynamics and thermodynamics without requiring any a priori knowledge of the relevant degrees of freedom. These results suggest the presence of a local mechanism for the high communication efficiency generally observed in complex systems.