Molecular dynamics simulation of protein denaturation: solvation of the hydrophobic cores and secondary structure of barnase

TitleMolecular dynamics simulation of protein denaturation: solvation of the hydrophobic cores and secondary structure of barnase
Publication TypeJournal Article
Year of Publication1994
AuthorsCaflisch A., Karplus M.
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue5
Pagination1746-1750
Date Published1994 Mar 1
Type of ArticleResearch Article
ISSN0027-8424
KeywordsBacillus, Models, Molecular, Molecular Structure, Protein Conformation, Protein Denaturation, Protein Structure, Secondary, Ribonucleases, Solvents, Thermodynamics
Abstract

The transition in barnase from the native state to a compact globule has been studied with high-temperature molecular dynamics simulations. A partial destruction of the α-helices and the outer strands of the β-sheet is observed with water molecules replacing the hydrogen bonds of the secondary structural elements. Simultaneously, the main α-helix moves away from the β-sheet and exposes the principal hydrophobic core, many of whose nonpolar side chains, beginning with the ones near the surface, become solvated by hydrogen-bonded water molecules. This step involves a significant increase in the solvent-exposed surface area; the resulting loss of stability due to the hydrophobic effect may be the major source of the activation barrier in the unfolding reaction. The detailed mechanism described here for the first stage of the denaturation of barnase, including the essential role of water molecules, is likely to be representative of protein denaturation, in general.

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Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID8127876
PubMed Central IDPMC43240
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