Use of Coarse-Grained and All-Atom Molecular Dynamics to Study Hsp70 and Hsp40 Chaperone Action
Pp. 23-46 (24)
Ewa I. Gołas, Magdalena A. Mozolewska, Paweł Krupa, Cezary Czaplewski, Harold A. Scheraga and Adam Liwo
The 70 kDalton (Hsp70) chaperones perform a variety of functions in living
cells, the most crucial being assisting correct protein folding, refolding misfolded
proteins, and participating in iron-sulfur cluster biogenesis. The chaperones consist of
the nucleotide-binding domain which, upon transitions between the ADP- to ATPbound
state, undergoes slight conformational changes, which trigger major
conformational changes in the conformation of the whole molecule, ultimately leading
to substrate binding or release. This chapter summarizes our work on the simulations of
the chaperone cycle by means of all-atom and coarse-grained molecular dynamics, and
on modeling the structure and interactions of two complexes that are formed during the
process of iron-sulfur biogenesis: the binary complex composed of the Iron-sulfur
protein 1 and the Jac1 Hsp40 cochaperone from yeast, and the ternary complex
composed of the Iron-sulfur protein 1, the Jac1 Hsp40 cochaperone, and the Stressseventy
subfamily Q protein 1 Hsp70 chaperone from yeast.
Hsp70 chaperones, Chaperone cycle, Iron-sulfur biogenesis,
Molecular modeling, Molecular dynamics.
Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland.