Protein conformational entropy is not slaved to water

Bryan S Marques,A Joshua Wand,Nathaniel V Nucci,Christine Jorge,Kathleen G Valentine,Matthew A Stetz

doi:10.1038/s41598-020-74382-5

Abstract

Conformational entropy can be an important element of the thermodynamics of protein functions such as the binding of ligands. The observed role for conformational entropy in modulating molecular recognition by proteins is in opposition to an often-invoked theory for the interaction of protein molecules with solvent water. The “solvent slaving” model predicts that protein motion is strongly coupled to various aspects of water such as bulk solvent viscosity and local hydration shell dynamics. Changes in conformational entropy are manifested in alterations of fast internal side chain motion that is detectable by NMR relaxation. We show here that the fast-internal side chain dynamics of several proteins are unaffected by changes to the hydration layer and bulk water. These observations indicate that the participation of conformational entropy in protein function is not dictated by the interaction of protein molecules and solvent water under the range of conditions normally encountered.

Highlights

Conformational entropy can be an important element of the thermodynamics of protein functions such as the binding of ligands
It is well established that water is a fundamental determinant of the structure and thermodynamic character of globular protein molecules, especially through the hydrophobic effect that arises from changes in the entropy of solvent water as the protein folds[1]
Solvent slaving posits that the majority of internal protein motion is dictated by various general structural and dynamic features of water. This view is seemingly at odds with the realization that fast internal protein motion is a manifestation of large reservoirs of conformational entropy that can greatly influence the thermodynamics of protein functions such as the binding of ligands[6] and the inherent stability of the folded s tate[7]

Summary

OPEN Protein conformational entropy is not slaved to water

We show here that the fast-internal side chain dynamics of several proteins are unaffected by changes to the hydration layer and bulk water These observations indicate that the participation of conformational entropy in protein function is not dictated by the interaction of protein molecules and solvent water under the range of conditions normally encountered. There is no apparent general correlation between local hydration dynamics at the surface of the protein and backbone or side chain motion (Fig. 2) These data collectively demonstrate that the conformational entropy of ubiquitin is largely independent of and certainly not dictated by either bulk or local hydration layer water dynamics. Squared generalized order parameters of amide NH (O2NH) (a) and methyl symmetry axis (O2axis) (b) of ubiquitin are plotted against the local hydration dynamics at the nearest amide NH as measured by the ratio of the NOE and ROE between the amide and water for the protein encapsulated within a reverse micelle. Anticipated to be independent of intracellular locale and is thereby free to convey entropically-mediated functional responses[6,10,38,39]

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