Critical structural fluctuations of proteins upon thermal unfolding challenge the Lindemann criterion

TitleCritical structural fluctuations of proteins upon thermal unfolding challenge the Lindemann criterion
Publication TypeJournal Article
Year of Publication2017
AuthorsKatava M, Stirnemann G, Zanatta M, Capaccioli S, Pachetti M, Ngai KL, Sterpone F, Paciaroni A
JournalProc Natl Acad Sci U S A
Volume114
Pagination9361-9366
Date PublishedAug
Keywordscell thermal stability, Lindemann criterion, Molecular Dynamics Simulation, neutron scattering, protein dynamics
Abstract

Internal subnanosecond timescale motions are key for the function of proteins, and are coupled to the surrounding solvent environment. These fast fluctuations guide protein conformational changes, yet their role for protein stability, and for unfolding, remains elusive. Here, in analogy with the Lindemann criterion for the melting of solids, we demonstrate a common scaling of structural fluctuations of lysozyme protein embedded in different environments as the thermal unfolding transition is approached. By combining elastic incoherent neutron scattering and advanced molecular simulations, we show that, although different solvents modify the protein melting temperature, a unique dynamical regime is attained in proximity of thermal unfolding in all solvents that we tested. This solvation shell-independent dynamical regime arises from an equivalent sampling of the energy landscape at the respective melting temperatures. Thus, we propose that a threshold for the conformational entropy provided by structural fluctuations of proteins exists, beyond which thermal unfolding is triggered.

DOI10.1073/pnas.1707357114
Citation Key2017|2025
PubMed ID28808004