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Thermal unfolding simulations of apo‐calmodulin using leap‐dynamics
Author(s) -
Kleinjung Jens,
Fraternali Franca,
Martin Stephen R.,
Bayley Peter M.
Publication year - 2003
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.10331
Subject(s) - molecular dynamics , calmodulin , protein folding , force field (fiction) , chemistry , chemical physics , crystallography , folding (dsp implementation) , physics , statistical physics , thermodynamics , computational chemistry , calcium , biochemistry , organic chemistry , quantum mechanics , electrical engineering , engineering
The simulation method leap‐dynamics (LD) has been applied to protein thermal unfolding simulations to investigate domain‐specific unfolding behavior. Thermal unfolding simulations of the 148‐residue protein apo‐calmodulin with implicit solvent were performed at temperatures 290 K, 325 K, and 360 K and compared with the corresponding molecular dynamics trajectories in terms of a number of calculated conformational parameters. The main experimental results of unfolding are reproduced in showing the lower stability of the C‐domain: at 290 K, both the N‐ and C‐domains are essentially stable; at 325 K, the C‐domain unfolds, whereas the N‐domain remains folded; and at 360 K, both domains unfold extensively. This behavior could not be reproduced by molecular dynamics simulations alone under the same conditions. These results show an encouraging degree of convergence between experiment and LD simulation. The simulations are able to describe the overall plasticity of the apo‐calmodulin structure and to reveal details such as reversible folding/unfolding events within single helices. The results show that by using the combined application of a fast and efficient sampling routine with a detailed molecular dynamics force field, unfolding simulations of proteins at atomic resolution are within the scope of current computational power. Proteins 2003;50:648–656. © 2003 Wiley‐Liss, Inc.