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Understanding the roles of amino acid residues in tertiary structure formation of chignolin by using molecular dynamics simulation
Author(s) -
Terada Tohru,
Satoh Daisuke,
Mikawa Tsutomu,
Ito Yutaka,
Shimizu Kentaro
Publication year - 2008
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/prot.22100
Subject(s) - molecular dynamics , energy landscape , chemistry , protein tertiary structure , amino acid , folding (dsp implementation) , crystallography , protein structure , nuclear magnetic resonance spectroscopy , hydrogen bond , molecule , chemical physics , stereochemistry , computational chemistry , biochemistry , organic chemistry , electrical engineering , engineering
Chignolin is a 10‐residue peptide (GYDPETGTWG) that forms a stable β‐hairpin structure in water. However, its design template, GPM12 (GYDDATKTFG), does not have a specific structure. To clarify which amino acids give it the ability to form the β‐hairpin structure, we calculated the folding free‐energy landscapes of chignolin, GPM12, and their chimeric peptides using multicanonical molecular dynamics (MD) simulation. Cluster analysis of the conformational ensembles revealed that the native structure of chignolin was the lowest in terms of free energy while shallow local minima were widely distributed in the free energy landscape of GPM12, in agreement with experimental observations. Among the chimeric peptides, GPM12(D4P/K7G) stably formed the same β‐hairpin structure as that of chignolin in the MD simulation. This was confirmed by nuclear magnetic resonance (NMR) spectroscopy. A comparison of the free‐energy landscapes showed that the conformational distribution of the Asp3‐Pro4 sequence was inherently biased in a way that is advantageous both to forming hydrogen bonds with another β‐strand and to initiating loop structure. In addition, Gly7 helps stabilize the loop structure by having a left‐handed α‐helical conformation. Such a conformation is necessary to complete the loop structure, although it is not preferred by other amino acids. Our results suggest that the consistency between the short‐range interactions that determine the local geometries and the long‐range interactions that determine the global structure is important for stable tertiary structure formation. Proteins 2008. © 2008 Wiley‐Liss, Inc.