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Exploring the energy landscape of a β hairpin in explicit solvent
Author(s) -
García Angel E.,
Sanbonmatsu Kevin Y.
Publication year - 2001
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/1097-0134(20010215)42:3<345::aid-prot50>3.0.co;2-h
Subject(s) - energy landscape , solvent , energy (signal processing) , computer science , chemistry , biological system , mathematics , biology , organic chemistry , biochemistry , statistics
We studied the energy landscape of the peptide Ace‐GEWTYDDATKTFTVTE‐Nme, taken from the C‐terminal fragment (41–56) of protein G, in explicit aqueous solution by a highly parallel replica‐exchange approach that combines molecular dynamics trajectories with a temperature exchange Monte Carlo process. The combined trajectories in T and configurational space allow a replica to overcome a free energy barrier present at one temperature by increasing T, changing configurations, and cooling in a self‐regulated manner, thus allowing sampling of broad regions of configurational space in short (nanoseconds) time scales. The free energy landscape of this system over a wide range of temperatures shows that the system preferentially adopts a beta hairpin structure. However, the peptide also samples other stable ensembles where the peptide adopts helices and helix‐turn‐helix states, among others. The helical states become increasingly stable at low temperatures, but are slightly less stable than the beta turn ensemble. The energy landscape is rugged at low T, where substates are separated by large energy barriers. These barriers disappear at higher T (∼330 K), where the system preferentially adopts a “molten globule” state with structures similar to the beta hairpin. Proteins 2001;42:345–354. © 2000 Wiley‐Liss, Inc.