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Atomistic detailed free‐energy landscape of intrinsically disordered protein studied by multi‐scale divide‐and‐conquer molecular dynamics simulation
Author(s) -
Shimoyama Hiromitsu,
Yonezawa Yasushige
Publication year - 2021
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.26429
Subject(s) - molecular dynamics , divide and conquer algorithms , homology modeling , crystallography , folding (dsp implementation) , chemistry , energy landscape , physics , computer science , computational chemistry , algorithm , biochemistry , electrical engineering , enzyme , engineering
Calcineurin (CaN) is a eukaryotic serine/threonine protein phosphatase activated by both Ca 2+ and calmodulin (CaM), including intrinsically disordered region (IDR). The region undergoes folding into an α‐helix form in the presence Ca 2+ ‐loaded CaM. To sample the ordered structure of the IDR by conventional all atom model (AAM) molecular dynamics (MD) simulation, the IDR and Ca 2+ ‐loaded CaM must be simultaneously treated. However, it is time‐consuming task because the coupled folding and binding should include repeated binding and dissociation. Then, in this study, we propose novel multi‐scale divide‐and‐conquer MD (MSDC‐MD), which combines AAM‐MD and coarse‐grained model MD (CGM‐MD). To speed up the conformation sampling, MSDC‐MD simulation first treats the IDR by CGM to sample conformations from wide conformation space; then, multiple AAM‐MD in a limited area is initiated using the resultant CGM conformation, which is reconstructed by homology modeling method. To investigate performance, we sampled the ordered conformation of the IDR using MSDC‐MD; the root‐mean‐square distance (RMSD) with respect to the experimental structure was 2.23 Å.