Molecular modeling of the binding modes of the iron-sulfur protein to the Jac1 co-chaperone from S accharomyces cerevisiae by all-atom and coarse-grained approaches

Abstract

The Iron sulfur protein 1 (Isu1) from yeast, and the J-type co-chaperone Jac1, 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 L105, L109, and Y163 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/MD simulations, to be involved in strong interactions between Isu1 and Jac1 in the complex. Moreover, N95, T98, P102, H112, V159, L167 and A170 of Jac1, not yet tested experimentally, were also found important in binding.

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Two MnII, CuII complexes derived from 3,5‐bis(1‐imidazoly) pyridine: Synthesis, DNA binding, Molecular docking and cytotoxicity studies

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Computational Studies of the Mechanical Stability for Single-Strand Break DNA

“…23,24 is a coarse-grained model for nucleic acids derived analogically to the physics-based coarse-grained model for proteins UNited RESidue (UNRES), which has been developed for over 20 years and used mostly to predict protein structure 25 and dynamics. 26…”