ABSTRACT:Computational tools have been widely utilized to design potent leads against specific targets as a part of drug discovery process. Moreover, virtual screening has been reported as an efficient concept in filtering actives from a huge library of compounds. In this paper, a computational approach employing virtual screening of Drug Bank database was implemented to dock 1400 drugs against caspase-3 to evaluate the binding affinities of ligands with the receptor. Docking analysis with Molegro Virtual Docker revealed top 10 drugs and hence consensus re-scoring was employed to obtain true hits. Classes were generated using rank-sum technique and the top five hits (Olmesartan, Verteporfin, Saprisartan, Atorvastatin and Lapatinib) were tested experimentally to determine the inhibitory effects on growth of HeLa cells in vitro. It was observed that proliferation of HeLa cells could be significantly inhibited by Atorvastatin in a concentration dependent manner.
KeyWords: Apoptosis, Caspase-3, Docking, carcinoma of cervix, MTT assay.
How to cite: Adinarayana et. al. Int J Computat Bioinfo and In Silico Model. 1(5) 2012: 55-57
ABSTRACT:Many proteins from structural genomics projects with known structure and unknown function are deposited in database as hypothetical proteins. Therefore, to predict the function of such proteins, various bioinformatics softwares and analysis tools can be utilized. In this work, hypothetical proteins are searched from a protein structure database, Protein Data Bank (PDB) and 1RW0 protein (243 residues) was selected and analysis was carried out by performing sequence similarity search against various databases like non-redundant database, reference database and swissprot database using blastp program of NCBI and homology was identified with tRNA methyltransferase. Further analysis was followed by multiple alignments that listed the residue conservation. The active site region of the protein was identified using CASTp server. Validation of the programs/softwares used in the analysis resulted in identification of 2HMA protein, a tRNA methyltransferase. Further, docking enzyme specific ligand SAM (S-adenosyl methionine) within the active site region of 1RW0 lead to specific study that shall be used to predict the function of the protein based on the residues (conserved vs mutated) that interact with the selected ligands.
ABSTRACT:Multiple sequence alignment program, Clustal W was employed to study the active site amino acid residue variations among human MAP kinases that participate in growth, stress and inflammatory related pathways. It was observed from analysis that the specificity of MAPKs participating in respective pathways is based on active site residue similarity and variant residue patterns. The analysis is further supported by domain region similarities using prosite database. Phylogenetic tree analysis and active site residue variations suggest that MAPK 12 and 13 are diverged from MAPK 11 and 14. Domain architecture data revealed that MAPK 4 and 6 are without Ser-Thr kinase domain and MAPK 8, 9 and 10 without ATP kinase domain. Our work emphasizes the use of computational tools and methods, like, multiple sequence alignment, phylogenetic tree analysis and domain analysis towards identification of MAP kinase protein specificity in respective pathways.
KeyWords: MAP Kinase, Clustal W, multiple sequence alignment, pathways, active site residues
How to cite: Colluru VTSS and Naishitha A. Int J Computat Bioinfo and In Silico Model. 1(5) 2012: 63-67