Molecular docking and High-throughput screening of potent inhibitor to gp46SU involved in ATLL through drug design studies

Barik, Manas Ranjan; Ranjan, K. Sahanmugha
June 2012
Journal of Chemical & Pharmaceutical Research;2012, Vol. 4 Issue 6, p3040
Academic Journal
Adult T-cell Leukemia/Lymphoma, a malignancy of mature activated T-cell is caused by the Human T cell Lymphotropic virus type 1(HTLV-1). HTLV-1 entry into the cell involves the interaction between the surface subunit and cellular receptor of the host. On the basis of studies carried by Kathryn.S and team on the functional domains of the HTLV-1 SU, we carried out computational drug designing and docking studies on HSPG binding domain of gp46SU of env protein. Structure modelling, analysis and validation was done for gp46SU. Scaffold selection was based on the functional properties of HSPG binding domain of the protein. Leads were identified based on several physiochemical properties and we created our library with those new molecules that were generated based on Lipinski's rule of five. We carried out high throughput screening and molecular docking on 446 molecules from scaffolds selected. Screening of molecules was based on the criterions such as, TOPKAT and ADMET properties. Among the ligands used, only three compounds were identified to have interaction within the targeted domain. Eleven molecules were analysed with positive docking results and interactions within the binding site. Pharmacophores were generated and analysed for selected drug candidates. The ranking of ligands helped in the identification of the best inhibitor(SH19 and SH226) that can better target gp46SU in an effective way. To be more specific about our drug candidate we suggest SH19 to be the most potent molecule in terms of physiochemical and docking properties. These results suggest that the identified compounds have the potential to inhibit HSPG binding in ATLL.


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