Linked Life Data

12581650

Source:http://linkedlifedata.com/resource/pubmed/id/12581650

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-2-12
pubmed:abstractText
What energetic and solvation effects underlie the remarkable two-state thermodynamics and folding/unfolding kinetics of small single-domain proteins? To address this question, we investigate the folding and unfolding of a hierarchy of continuum Langevin dynamics models of chymotrypsin inhibitor 2. We find that residue-based additive G?-like contact energies, although native-centric, are by themselves insufficient for protein-like calorimetric two-state cooperativity. Further native biases by local conformational preferences are necessary for protein-like thermodynamics. Kinetically, however, even models with both contact and local native-centric energies do not produce simple two-state chevron plots. Thus a model protein's thermodynamic cooperativity is not sufficient for simple two-state kinetics. The models tested appear to have increasing internal friction with increasing native stability, leading to chevron rollovers that typify kinetics that are commonly referred to as non-two-state. The free energy profiles of these models are found to be sensitive to the choice of native contacts and the presumed spatial ranges of the contact interactions. Motivated by explicit-water considerations, we explore recent treatments of solvent granularity that incorporate desolvation free energy barriers into effective implicit-solvent intraprotein interactions. This additional feature reduces both folding and unfolding rates vis-à-vis that of the corresponding models without desolvation barriers, but the kinetics remain non-two-state. Taken together, our observations suggest that interaction mechanisms more intricate than simple G?-like constructs and pairwise additive solvation-like contributions are needed to rationalize some of the most basic generic protein properties. Therefore, as experimental constraints on protein chain models, requiring a consistent account of protein-like thermodynamic and kinetic cooperativity can be more stringent and productive for some applications than simply requiring a model heteropolymer to fold to a target structure.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
326
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
911-31
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Solvation effects and driving forces for protein thermodynamic and kinetic cooperativity: how adequate is native-centric topological modeling?
pubmed:affiliation
Department of Biochemistry, Protein Engineering Network of Centres of Excellence (PENCE), Faculty of Medicine, University of Toronto, Toronto, Ont., Canada M5S 1A8.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't