Protein-Folding Landscapes in Multi-Chain Systems

Journal Article · Mon Jun 20 04:00:00 EDT 2005 · Proceedings of National Academy of Sciences

DOI:https://doi.org/10.1073/pnas.0505342102· OSTI ID:861262

Cellmer, Troy; Bratko, Dusan; Prausnitz, John M; Blanch, Harvey

Computational studies of proteins have significantly improved our understanding of protein folding. These studies are normally carried out using chains in isolation. However, in many systems of practical interest, proteins fold in the presence of other molecules. To obtain insight into folding in such situations, we compare the thermodynamics of folding for a Miyazawa-Jernigan model 64-mer in isolation to results obtained in the presence of additional chains. The melting temperature falls as the chain concentration increases. In multi-chain systems, free-energy landscapes for folding show an increased preference for misfolded states. Misfolding is accompanied by an increase in inter-protein interactions; however, near the folding temperature, the transition from folded chains to misfolded and associated chains isentropically driven. A majority of the most probable inter-protein contacts are also native contacts, suggesting that native topology plays a role in early stages of aggregation.

• Research Organization: Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
• Sponsoring Organization: USDOE Director. Office of Science. Office of Basic EnergySciences; National Science Foundation
• DOE Contract Number: AC02-05CH11231
• OSTI ID: 861262
• Report Number(s): LBNL--57925; BnR: KC0302040
• Journal Information: Proceedings of National Academy of Sciences, Journal Name: Proceedings of National Academy of Sciences Journal Issue: 33 Vol. 102
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
FREE ENERGY
MELTING
PROTEINS
THERMODYNAMICS
TOPOLOGY
protein folding protein aggregation computersimulation