Homology modeling and drug designing of 18KDA antigen in mycobacterium leprae.

ABSTRACT

Most of the antigens of Mycobacterium leprae that have been identified are members of stress protein families. 18kDa antigen of M. leprae is an important antigen in the immune response to leprosy. This protein antigen of M. leprae is related to the family of small heat shock protein. To predict the structure of 18kDa antigen and to understand the mechanisms of inhibitors interaction, a threedimensional model was generated based on the Crystal Structure and assembly of eukaryotic small heat shock protein (PDB 1GME) by using MODELLER7v7. The structure having a least modeller objective function was used as a starting point for picoseconds-duration molecular dynamics simulations. With the aid of the molecular dynamics and minimization methods, the final refined model was obtained and was further assessed by ERRAT, WHATCHECK and PROCHECK, which suggested that the refined model was reliable. Docking studies were performed by using the models with 2-mercaptoethanol and 3-amino- 5-methylhexanoic acid inhibitors. The results indicate that the 3-amino-5,5-diphenylpentanoic acid has more affinity than the other drug derivatives. The docking studies also suggest that MET-03, ARG-04, ASP-31, ALA-32, TRP-33, ARG-34, GLU-35 ARG-89, GLN-90 LEU-91 and VAL-92 are important determinant residues in binding with ligands. From the docking studies, we also suggest that GLU-35, in 18kDa protein domain is an important residue in binding.