Homology modeling, ligand docking and in silico mutagenesis of neurospora Hsp80 (90): insight into intrinsic ATPase activity

► We created homology-based models of full-length Hsp90s from N. crassa and S. cerevisiae. ► Experimental data guided our reconstruction of flexible regions in both proteins. ► A novel multi-domain interaction near the C-terminus of Hsp90 dimers was uncovered. ► The structural basis of differences in ATPase activity of fungal Hsp90s was studied. ► Binding to ATP, but not ADP, is affected by sequence of the 'lid' region in Hsp90s.