Coarse-grained strategy for modeling protein stability in concentrated solutions. II: phase behavior

Coarse-grained strategy for modeling protein stability in concentrated solutions. II: phase behavior
Engineering Village 2
2006 Elsevier Inc.
Accession number: 8924818

Title: Coarse-grained strategy for modeling protein stability in concentrated solutions. II: phase behavior

Authors: Shen, V.K.1 ; Cheung, J.K.; Errington, J.R.; Truskett, T.M.

Author affiliation: 1 Div. of Phys. & Chem. Properties, Nat. Inst. of Stand. & Technol., Gaithersburg, MD, USA

Serial title: Biophysical Journal

Abbreviated serial title: Biophys. J. (USA)

Volume: 90

Issue: 6

Publication date: 15 March 2006

Pages: 1949-60

Language: English

ISSN: 0006-3495


Document type: Journal article (JA)

Publisher: Biophys. Soc

Country of publication: USA

Material Identity Number: B154-2006-006

Abstract: We use highly efficient transition-matrix Monte Carlo simulations to determine equilibrium unfolding curves and fluid phase boundaries for solutions of coarse-grained globular proteins. The model we analyze derives the intrinsic stability of the native state and protein-protein interactions from basic information about protein sequence using heteropolymer collapse theory. It predicts that solutions of low hydrophobicity proteins generally exhibit a single liquid phase near their midpoint temperatures for unfolding, while solutions of proteins with high sequence hydrophobicity display the type of temperature-inverted, liquid-liquid transition associated with aggregation processes of proteins and other amphiphilic molecules. The phase transition occurring in solutions of the most hydrophobic protein we study extends below the unfolding curve, creating an immiscibility gap between a dilute, mostly native phase and a concentrated, mostly denatured phase. The results are qualitatively consistent with the solution behavior of hemoglobin (HbA) and its sickle variant (HbS), and they suggest that a liquid-liquid transition resulting in significant protein denaturation should generally be expected on the phase diagram of high-hydrophobicity protein solutions. The concentration fluctuations associated with this transition could be a driving force for the nonnative aggregation that can occur below the midpoint temperature

Number of references: 107

Inspec controlled terms: aggregation - biochemistry - molecular biophysics - Monte Carlo methods - phase diagrams - physiological models - proteins - solubility

Uncontrolled terms: coarse-grained globular proteins - protein stability modeling - concentrated solutions - phase behavior - transition-matrix Monte Carlo simulations - equilibrium unfolding curves - fluid phase boundaries - protein-protein interactions - protein sequence - heteropolymer collapse theory - temperature-inverted liquid-liquid transition - aggregation - phase transition - immiscibility gap - hemoglobin - sickle hemoglobin - protein denaturation - phase diagram - concentration fluctuations

Inspec classification codes: A8715D Physical chemistry of biomolecular solutions; condensed states - A8715B Biomolecular structure, configuration, conformation, and active sites - A8710 General, theoretical, and mathematical biophysics - A3620E Macromolecular constitution (chains and sequences) - A0250 Probability theory, stochastic processes, and statistics - A0540 Fluctuation phenomena, random processes, and Brownian motion - A8270 Disperse systems

Treatment: Theoretical or Mathematical (THR)

Discipline: Physics (A)

DOI: 10.1529/biophysj.105.076497

Database: Inspec

Copyright 2006, The Institution of Engineering and Technology
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