Thermodynamics of folding and association of lattice-model proteins - Analytical Methods & Tools for Lyophilization

Thermodynamics of folding and association of lattice-model proteins
Engineering Village 2
2006 Elsevier Inc.
Accession number: 8419399

Title: Thermodynamics of folding and association of lattice-model proteins

Authors: Cellmer, T.1 ; Bratko, D.; Prausnitz, J.M.; Blanch, H.

Author affiliation: 1 Dept. of Chem. Eng., Univ. of California, Berkeley, CA, USA

Serial title: Journal of Chemical Physics

Abbreviated serial title: J. Chem. Phys. (USA)

Volume: 122

Issue: 17

Publication date: 1 May 2005

Pages: 174908-1-11

Language: English

ISSN: 0021-9606

CODEN: JCPSA6

Document type: Journal article (JA)

Publisher: AIP

Country of publication: USA

Material Identity Number: J008-2005-013

Abstract: Closely related to the "protein folding problem" is the issue of protein misfolding and aggregation. Protein aggregation has been associated with the pathologies of nearly 20 human diseases and presents serious difficulties during the manufacture of pharmaceutical proteins. Computational studies of multiprotein systems have recently emerged as a powerful complement to experimental efforts aimed at understanding the mechanisms of protein aggregation. We describe the thermodynamics of systems containing two lattice-model 64-mers. A parallel tempering algorithm abates problems associated with glassy systems and the weighted histogram analysis method improves statistical quality. The presence of a second chain has a substantial effect on single-chain conformational preferences. The melting temperature is substantially reduced, and the increase in the population of unfolded states is correlated with an increase in interactions between chains. The transition from two native chains to a non-native aggregate is entropically favorable. Non-native aggregates receive ~25% of their stabilizing energy from intraprotein contacts not found in the lowest-energy structure. Contact maps show that for non-native dimers, nearly 50% of the most probable interprotein contacts involve pairs of residues that form native contacts, suggesting that a domain-swapping mechanism is involved in self-association

Number of references: 36

Inspec controlled terms: aggregation - association - entropy - macromolecules - molecular biophysics - proteins

Uncontrolled terms: thermodynamics - lattice-model proteins - protein folding problem - protein misfolding - protein aggregation - human diseases - pharmaceutical proteins - computational studies - multiprotein systems - lattice-model - parallel tempering algorithm - glassy systems - weighted histogram analysis method - statistical quality - second chain - single-chain conformation - melting temperature - native chains - nonnative aggregate - entropy - stabilizing energy - intraprotein contacts - domain-swapping mechanism - self-association

Inspec classification codes: A8715B Biomolecular structure, configuration, conformation, and active sites - A3620C Macromolecular conformation (statistics and dynamics) - A3620E Macromolecular constitution (chains and sequences) - A8715P Model reactions in molecular biophysics

Treatment: Theoretical or Mathematical (THR)

Discipline: Physics (A)

DOI: 10.1063/1.1888545

Database: Inspec

Copyright 2005, IEE
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