Nonlinear excitations match correlated motions unveiled by NMR in proteins: a new perspective on allosteric cross-talk

Abstract

In this paper we propose a novel theoretical framework for interpreting long-range dynamical correlations unveiled in proteins through NMR measurements. The theoretical rationale relies on the hypothesis that correlated motions in proteins may be reconstructed as large-scale, collective modes sustained by long-lived nonlinear vibrations known as discrete breathers (DB) localized at key, hot-spot sites. DBs are spatially localized modes, whose nonlinear nature hinders resonant coupling with the normal modes, thus conferring them long lifetimes as compared to normal modes. DBs have been predicted to exist in proteins, localized at few $hotspot$ residues typically within the stiffest portions of the structure. We compute DB modes analytically in the framework of the nonlinear network model, showing that the displacement patterns of many DBs localized at key sites match to a remarkable extent the experimentally uncovered correlation blueprint. The computed dispersion relations prove that it is physically possible for some of these DBs to be excited out of thermal fluctuations at room temperature. Based on our calculations, we speculate that transient energy redistribution among the vibrational modes in a protein might favor the emergence of DB-like bursts of long-lived energy at hot-spot sites with lifetimes in the ns range, able to sustain critical, function-encoding correlated motions. More generally, our calculations provide a novel quantitative tool to predict fold-spanning dynamical pathways of correlated residues that may be central to allosteric cross-talk in proteins.