First-principles calculation of the folding free energy of a three-helix bundle protein.

Autor: Boczko EM; Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA., Brooks CL 3rd
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 1995 Jul 21; Vol. 269 (5222), pp. 393-6.
DOI: 10.1126/science.7618103
Abstrakt: The folding and unfolding of a three-helix bundle protein were explored with molecular-dynamics simulations, cluster analysis, and weighted-histogram techniques. The folding-unfolding process occurs by means of a "folding funnel," in which a uniform and broad distribution of conformational states is accessible outside of the native manifold. This distribution narrows near a transition region and becomes compact within the native manifold. Key thermodynamic steps in folding include initial interactions around the amino-terminal helix-turn-helix motif, interactions between helices I and II, and, finally, the docking of helix III onto the helix I-II subdomain. A metastable minimum in the calculated free-energy surface is observed at approximately 1.5 times the native volume. Folding-unfolding thermodynamics are dominated by the opposing influences of protein-solvent energy, which favors unfolding, and the overall entropy, which favors folding by means of the hydrophobic effect.
Databáze: MEDLINE