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Transition state of a SH3 domain detected with principle component analysis and a charge‐neutralized all‐atom protein model
Author(s) -
Mitomo Daisuke,
Nakamura Hironori K.,
Ikeda Kazuyoshi,
Yamagishi Akihiko,
Higo Junichi
Publication year - 2006
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.21069
Subject(s) - radius of gyration , atom (system on chip) , crystallography , molecular dynamics , chemistry , energy profile , gyration , sh3 domain , molecular physics , energy (signal processing) , physics , computational chemistry , geometry , polymer , quantum mechanics , biochemistry , mathematics , organic chemistry , kinase , proto oncogene tyrosine protein kinase src , computer science , embedded system
The src SH3 domain has been known to be a two‐state folder near room temperature. However, in a previous study with an all‐atom model simulation near room temperature, the transition state of this protein was not successfully detected on a free‐energy profile using two axes: the radius of gyration ( R g ) and native contact reproduction ratio ( Q value). In this study, we focused on an atom packing effect to characterize the transition state and tried another analysis to detect it. To explore the atom packing effect more efficiently, we introduced a charge‐neutralized all‐atom model, where all of the atoms in the protein and water molecules were treated explicitly, but their partial atomic charges were set to zero. Ten molecular dynamics simulations were performed starting from the native structure at 300 K, where the simulation length of each run was 90 ns, and the protein unfolded in all runs. The integrated trajectories (10 × 90 = 900 ns) were analyzed by a principal component analysis (PCA) and showed a clear free‐energy barrier between folded‐ and unfolded‐state conformational clusters in a conformational space generated by PCA. There were segments that largely deformed when the conformation passed through the free‐energy barrier. These segments correlated well with the structural core regions characterized by large ϕ‐values, and the atom‐packing changes correlated with the conformational deformations. Interestingly, using the same simulation data, no significant barrier was found in a free‐energy profile using the R g and Q values for the coordinate axes. These results suggest that the atom packing effect may be one of the most important determinants of the transition state. Proteins 2006. © 2006 Wiley‐Liss, Inc.