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Molecular modeling of the binding modes of the iron‐sulfur protein to the J ac1 co‐chaperone from S accharomyces cerevisiae by all‐atom and coarse‐grained approaches
Author(s) -
Mozolewska Magdalena A.,
Krupa Paweł,
Scheraga Harold A.,
Liwo Adam
Publication year - 2015
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.24824
Subject(s) - molecular dynamics , docking (animal) , chaperone (clinical) , autodock , biogenesis , homology modeling , force field (fiction) , chemistry , crystallography , biophysics , computational chemistry , biochemistry , physics , biology , enzyme , nursing , medicine , pathology , quantum mechanics , in silico , gene
The iron‐sulfur protein 1 (Isu1) and the J‐type co‐chaperone Jac1 from yeast are part of a huge ATP‐dependent system, and both interact with Hsp70 chaperones. Interaction of Isu1 and Jac1 is a part of the iron‐sulfur cluster biogenesis system in mitochondria. In this study, the structure and dynamics of the yeast Isu1–Jac1 complex has been modeled. First, the complete structure of Isu1 was obtained by homology modeling using the I‐TASSER server and YASARA software and thereafter tested for stability in the all‐atom force field AMBER. Then, the known experimental structure of Jac1 was adopted to obtain initial models of the Isu1–Jac1 complex by using the ZDOCK server for global and local docking and the AutoDock software for local docking. Three most probable models were subsequently subjected to the coarse‐grained molecular dynamics simulations with the UNRES force field to obtain the final structures of the complex. In the most probable model, Isu1 binds to the left face of the Γ‐shaped Jac1 molecule by the β‐sheet section of Isu1. Residues L 105 , L 109 , and Y 163 of Jac1 have been assessed by mutation studies to be essential for binding (Ciesielski et al ., J Mol Biol 2012; 417:1–12). These residues were also found, by UNRES/molecular dynamics simulations, to be involved in strong interactions between Isu1 and Jac1 in the complex. Moreover, N 95 , T 98 , P 102 , H 112 , V 159 , L 167 , and A 170 of Jac1, not yet tested experimentally, were also found to be important in binding. Proteins 2015; 83:1414–1426. © 2015 Wiley Periodicals, Inc.