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Atomistic detailed free-energy landscape of intrinsically disordered protein studied by multi-scale divide-and-conquer molecular dynamics simulation.
- Source :
-
Journal of computational chemistry [J Comput Chem] 2021 Jan 05; Vol. 42 (1), pp. 19-26. Date of Electronic Publication: 2020 Oct 08. - Publication Year :
- 2021
-
Abstract
- Calcineurin (CaN) is a eukaryotic serine/threonine protein phosphatase activated by both Ca <superscript>2+</superscript> and calmodulin (CaM), including intrinsically disordered region (IDR). The region undergoes folding into an α-helix form in the presence Ca <superscript>2+</superscript> -loaded CaM. To sample the ordered structure of the IDR by conventional all atom model (AAM) molecular dynamics (MD) simulation, the IDR and Ca <superscript>2+</superscript> -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.<br /> (© 2020 Wiley Periodicals LLC.)
Details
- Language :
- English
- ISSN :
- 1096-987X
- Volume :
- 42
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of computational chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33030249
- Full Text :
- https://doi.org/10.1002/jcc.26429