  The heat shock organizing protein (Hop) is important in modulating the
activity and co-interaction of two chaperones: heat shock protein 70 and 90
(Hsp70 and Hsp90). Recent research suggested that Plasmodium falciparum Hop
(PfHop), PfHsp70 and PfHsp90 form a complex in the trophozoite infective stage.
However, there has been little computational research on the malarial Hop
protein in complex with other malarial Hsps. Using in silico characterization
of the protein, this work showed that individual domains of Hop are evolving at
different rates within the protein. Differences between human Hop (HsHop) and
PfHop were identified by motif analysis. Homology modeling of PfHop and HsHop
in complex with their own cytosolic Hsp90 and Hsp70 C-terminal peptide partners
indicated excellent conservation of the Hop concave TPR sites bound to the
C-terminal motifs of partner proteins. Further, we analyzed additional binding
sites between Hop and Hsp90, and showed, for the first time, that they are
distinctly less conserved between human and malaria parasite. These sites are
located on the convex surface of Hop TPR2, and involved in interactions with
the Hsp90 middle domain. Since the convex sites are less conserved than the
concave sites, it makes their potential for malarial inhibitor design extremely
attractive (as opposed to the concave sites which have been the focus of
previous efforts).
