FUNCTIONAL ANNOTATION AND SEQUENCE ANALYSIS OF PROTEIN BAH104511.1 FOR HOMOLOGY MODELING TO FIND POTENTIAL BINDERS BY VIRTUAL SCREENING AND DOCKING ANALYSIS

Abstract

A protein with Accession No. BAH14511.1 isolated form tongue tumor tissue of Homo sapiens was taken. Non-redundant BLAST revealed this protein to be identical with cGMPdependent protein kinase II isoform b for which the sequence has been put online at NCBI site recently. PKGII has been reported to be very important for the regulation of different signalling pathways related to cancer and hence, prediction of the structure of PKGIIb would be important for finding potential binders that can further be used for the purpose of designing a drug that might help in the regulation of PKGIIb. For functional annotation, PROTPARAM, SMART, TMHMM, SignalP, SecretomeP, NetChop and NetPhos were used. BLAST against PDB entries was used to find out any homologs for which secondary and tertiary structures were compared with that of the protein by using different tools before homology modelling. The 3D structure predicted by Homology Modelling was validated by Verify3D and WhatIF. The binding site was predicted by using SiteMap which gives 5 sites but top scoring site was used. It was used for virtual screening to find structures that might act as ligands for it. This was done by using two- Schrödinger Fragments and NCI database. Many chemical structures were formed by different combinations of the fragments in Schrödinger Fragments which were then virtually screened. The virtual screening of Schrödinger fragments revealed that many chemical structures docked with the protein had a score of less than even -9.000 and were found to be following Lipinski’s Rule. The predicted protein 3D structure was also used for docking to chemical structures of NCI database with docking score as less as -12.547 which correspond to a good docking. The top 5 structures, each from compounds made from Schrödinger fragments and NCI database, having lowest docking scores have been found as potential binders for the protein.