Nonlinear backbone torsional pair correlations in proteins.

Pu Tian,Shiyang Long

doi:10.1038/srep34481

Abstract

Protein allostery requires dynamical structural correlations. Physical origin of which, however, remain elusive despite intensive studies during last two and half decades. Based on analysis of molecular dynamics (MD) simulation trajectories for ten proteins with different sizes and folds, we found that nonlinear backbone torsional pair (BTP) correlations, which are mainly spatially long-ranged and are dominantly executed by loop residues, exist extensively in most analyzed proteins. Examination of torsional motion for correlated BTPs suggested that such nonlinear correlations are mainly associated aharmonic torsional state transitions and in some cases strongly anisotropic local torsional motion of participating torsions, and occur on widely different and relatively longer time scales. In contrast, correlations between backbone torsions in stable α helices and β strands are mainly linear and spatially short-ranged, and are more likely to associate with harmonic local torsional motion. Further analysis revealed that the direct cause of nonlinear contributions are heterogeneous linear correlations. These findings implicate a general search strategy for novel allosteric modulation sites of protein activities.

Highlights

Based on analysis of molecular dynamics (MD) simulation trajectories for ten proteins with different sizes and folds, we found that nonlinear backbone torsional pair (BTP) correlations, which are mainly spatially long-ranged and are dominantly executed by loop residues, exist extensively in most analyzed proteins
We analyzed extensive MD simulation trajectories for ten proteins of different sizes and folds, and found that significant spatially long-ranged (SLR) nonlinear BTP correlations exist in most of studied proteins. Such nonlinear correlations are predominantly executed by loop residues and mainly associate with aharmonic torsional state transitions of participating torsions, which occur on widely different and relatively long time scales
Nonlinear correlations in limited cases may associate with strongly anisotropic local torsional motion

Summary

Introduction

Based on analysis of molecular dynamics (MD) simulation trajectories for ten proteins with different sizes and folds, we found that nonlinear backbone torsional pair (BTP) correlations, which are mainly spatially long-ranged and are dominantly executed by loop residues, exist extensively in most analyzed proteins. We focus on molecular motions that underly backbone torsional pair (BTP) correlations After calculating both mutual information and linear correlations for BTPs in extensive MD simulation trajectories of ten proteins with different sizes and folds (Fig. 1), we analyzed variation of correlations as a function of sequential and spatial distances, of belonging secondary structures, and of torsional motions and time scales. Nonlinear correlations occur for both spatially short and long-ranged BTPs, they mainly associate with aharmonic torsional state transitions on widely different and relatively longer time scales, and are dominantly executed by loop residues. The direct cause of nonlinear BTP correlations are found to be heterogeneous linear correlations associated with different torsional states or strongly anisotropic local motion of participating torsions

Methods

Results

Conclusion