Computational Elucidation of Interface Site Interaction Studies of Ldiscsglu۴۰۹&Glu۳۴۷ and Ldiscuarg۴۹&Lys۱۴۹ of the Iron-Sulphur Cluster Assembly Proteins: An Implication for Designing of Novel Therapeutic Strategies

Leishmaniasis is a rare tropical disease that causes severe loss of life and this causes a significant burden to all developing countries, including Indian subcontinents. A regulatory system occurs inside the parasitic organism that contains Iron-containing enzymes (LdIscU and LdIscS) for survival activities. Here we generated the homology model of these two proteins and the generated model and selection of the best model structure validated by the Ramachandran plot is found to be ۹۸.۰% residues are in the energetically most favoured region and LdIscS has ۹۴.۴% residues in the favoured area, (۴.۲%) residues in the allowed region, and ۱.۴ % (۶) residues in the disallowed region. The result suggested that the interacting amino acids involved in the interaction between two proteins are (LdIscS protein) are Gln۴۲۹, Leu۴۲۱, Ser۴۲۲, Val۳۴۶, Glu۳۸۵, Cys۳۴۵, Ser۳۴, Arg۳۱۳, Arg۳۲۱, Asn۳۸۶, Leu۴۲۴ and Trp۴۲۵ with Arg۳۲, Lys۱۴۲, Lys۱۴۷, Ser۱۴۸, Lys۱۴۹, Ser۱۵۱, Glu۵۳, Gly۵۵, Thr۴۶ and Ala۱۳۴ amino acids of LdIscU protein. Salt bridge interaction analysis also revealed the interacting amino acids of LdIscS are Glu۴۰۹ with Arg۴۹ of LdIscU (۴.۳۱ Å) and LdIscS of GLU۳۴۷ with LYS۱۴۹ of LdIscU (۴.۸۰ Å) have strong interaction between assembly essential proteins for the successful transfer of ions. The MD simulations studies suggested that these two interacting proteins forms the stable complex. The PCA analysis result suggests that the PC۱, PC۲ and PC۳ for LdIscS accounted for ۳۸.۰۷%, ۷.۸۹% and ۸.۵۷% of the variance, respectively, whereas the other PCs each contributed less than ۸%.

کلیدواژه ها:

Iron-Sulphur Cluster ، LdIscU ، LdIscS ، Protein-protein interaction ، Molecular docking ، Leishmaniasis