Topology, landscapes, and biomolecular energy transport

Justin E Elenewski,Kirill A Velizhanin,Michael Zwolak

doi:10.1038/s41467-019-12700-w

Abstract

While ubiquitous, energy redistribution remains a poorly understood facet of the nonequilibrium thermodynamics of biomolecules. At the molecular level, finite-size effects, pronounced nonlinearities, and ballistic processes produce behavior that diverges from the macroscale. Here, we show that transient thermal transport reflects macromolecular energy landscape architecture through the topological characteristics of molecular contacts and the nonlinear processes that mediate dynamics. While the former determines transport pathways via pairwise interactions, the latter reflects frustration within the landscape for local conformational rearrangements. Unlike transport through small-molecule systems, such as alkanes, nonlinearity dominates over coherent processes at even quite short time- and length-scales. Our exhaustive all-atom simulations and novel local-in-time and space analysis, applicable to both theory and experiment, permit dissection of energy migration in biomolecules. The approach demonstrates that vibrational energy transport can probe otherwise inaccessible aspects of macromolecular dynamics and interactions that underly biological function.

Highlights

While ubiquitous, energy redistribution remains a poorly understood facet of the nonequilibrium thermodynamics of biomolecules
We initiate our investigations using a series of replica-exchange molecular dynamics (REMD) simulations, as the lack of symmetries, granularity, and high-dimensional free energy landscapes of biomolecules necessitate an exhaustive exploration of conformational space[40,41,42]
We initiate non-equilibrium molecular dynamics (NEMD) simulations in a manner that mimics photoexcitation, distributing ≈1.6 eV of energy

Summary

Introduction

Energy redistribution remains a poorly understood facet of the nonequilibrium thermodynamics of biomolecules. Fourier’s law, J = −κ∇T and its time–dependent version capture diffusive heat flow, given by the flux J, in response to a temperature gradient ∇T Those two quantities are related by the thermal conductivity κ (or the diffusivity D), which can be anisotropic. Departures from a simple realization of Fourier’s law happen at large temperature gradients, beyond about 15 K/residue, even though transport is still diffusive The identification of these regimes is not possible through all-atom molecular dynamics alone[20,21,22,23,30,31,32] or normal-mode analysis (even when treating anharmonicity as a correction)[33,34,35,36,37,38,39]. We further demonstrate how the graph–theoretic topology of molecular contacts can define directed pathways for molecular energy redistribution

Methods

Results

Conclusion