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Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):9361-9366. doi: 10.1073/pnas.1707357114. Epub 2017 Aug 14.

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

Author information

1
Laboratoire de Biochimie Théorique, Institut de Biologie Physico-Chimique, CNRS Unité Propre de Recherche 9080, Université Paris Diderot, Sorbonne Paris Cité, 75005 Paris, France.
2
Dipartimento di Informatica, Università di Verona, 37134 Verona, Italy.
3
Dipartimento di Fisica, Università di Pisa and Istituto per i Processi Chimico-Fisici-Consiglio Nazionale delle Ricerche, 56127 Pisa, Italy.
4
Laboratoire de Biochimie Théorique, Institut de Biologie Physico-Chimique, CNRS Unité Propre de Recherche 9080, Université Paris Diderot, Sorbonne Paris Cité, 75005 Paris, France; alessandro.paciaroni@unipg.it fabio.sterpone@ibpc.fr.
5
Dipartimento di Fisica e Geologia, Università di Perugia, 06123 Perugia, Italy alessandro.paciaroni@unipg.it fabio.sterpone@ibpc.fr.

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.

KEYWORDS:

Lindemann criterion; cell thermal stability; molecular dynamics simulation; neutron scattering; protein dynamics

PMID:
28808004
PMCID:
PMC5584445
DOI:
10.1073/pnas.1707357114
[Indexed for MEDLINE]
Free PMC Article

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