Adhesive-cohesive model for protein compressibility: an alternative perspective on stability.

Abstract:

:As a dynamic property of folded proteins, protein compressibility provides important information about the forces that govern structural stability. We relate intrinsic compressibility to stability by using molecular dynamics to identify a molecular basis for the variation in compressibility among globular proteins. We find that excess surface charge accounts for this variation not only for the proteins simulated by molecular dynamics but also for a larger set of globular proteins. This dependence on charge distribution forms the basis for an adhesive-cohesive model of protein compressibility in which attractive forces from solvent compete with tertiary interactions that favor folding. Further, a newly recognized correlation between compressibility and the heat capacity of unfolding infers a link between compressibility and the enthalpy of unfolding. This linkage, together with the adhesive-cohesive model for compressibility, leads to the conclusion that folded proteins can gain enthalpic stability from a uniform distribution of charged atoms, as opposed to partitioning charge to the protein surface. Whether buried charged groups can be energetically stabilizing is a fundamental, yet controversial, question regarding protein structure. The analysis reported here implies that one mechanism to gain enthalpic stability involves positioning charge inside the protein in an optimal structural arrangement.

authors

Dadarlat VM,Post CB

doi

10.1073/pnas.2434157100

keywords:

subject

Has Abstract

pub_date

2003-12-09 00:00:00

pages

14778-83

issue

25

eissn

0027-8424

issn

1091-6490

pii

2434157100

journal_volume

100

pub_type

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