Computer modeling of small heat-shock metalloprotease of the human malariaparasite Plasmodium vivax

We present here computer generated model of N-terminal fragment, amino acid s (aa) 36-245, of a Plasmodium vivax heat shock metalloprotease called PVHS P28, whose gene was cloned and characterised earlier (1,2). The fragment sh owed homology with HSPs from many organisms, including Escherichia coli and Haemophilus influenzae. PVHSP28 had the signature sequence 'HEXXH' and 'EX XXD' of Zinc metalloproteases. Being the first malarial HSP possessing meta lloprotease activity, PVHSP28 is an ideal target for the design of new anti -malarial drugs. However, except for a small region (aa 62-132) which had 2 4.6% sequence similarity with ITAQ (a DNA polymerase), it did not show sequ ence similarity with any published structures in protein data bank. Hence i t could not be modelled using any automated modeling programs. We modelled 36-245 aa of PVHSP28 using predicted secondary structure as well as experim entally determined and predicted properties of the protein on the basis of its amino acid sequence, using various Internet tools and in-house package MODEL. The model was energy minimised using Sander's module of AMBER 5.0, w orking on a Silicon Graphics machine, with all atom force field.