Dynamics of the full-length yeast Hsp90 dimer

The Hsp90 chaperone is a complex homodimeric biological assembly that assists in the folding of proteins. It can undergo global conformational changes between an open (Adenosindiphosphat, ADP-bound) and closed (Adenosintriphosphat, ATP-bound) state that are of functional importance. How the conformational transitions are triggered and coupled to chaperone function is not well understood. Molecular dynamics simulations in explicit solvent starting from either the closed conformation or the open conformation in different nucleotide bound states and in the apo (without nucleotide) state were performed. On the time scale of ~300 ns the simulations starting from the closed state stayed close to the starting conformation independent of the nucleotide bound state. In case of the open structure the simulations indicated large global fluctuations including movements towards a more closed state, however, no complete transitions to the closed state were observed. The analysis of conformational fluctuations indicates only modest differences in local fluctuations of the monomers for open vs. closed state and global dimer changes are mediated by small local motions of the C-terminal Hsp90 segments