Sakharkar,Meena Kishore
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Publication Biocomputational strategies for microbial drug target identification.(2008) Sakharkar, K.R.; Sakharkar, M.K.; Chow, V.T.; NATIONAL UNIVERSITY MEDICAL INSTITUTES; BIOINFORMATICS CENTREThe complete genome sequences of about 300 bacteria (mostly pathogenic) have been determined, and many more such projects are currently in progress. The detection of bacterial genes that are non-homologous to human genes and are essential for the survival of the pathogen represent a promising means of identifying novel drug targets. We present a subtractive genomics approach for the identification of putative drug targets in microbial genomes and demonstrate its execution using Pseudomonas aeruginosa as an example. The resultant analyses are in good agreement with the results of systematic gene deletion experiments. This strategy enables rapid potential drug target identification, thereby greatly facilitating the search for new antibiotics. It should be recognized that there are limitations to this computational approach for drug target identification. Distant gene relationships may be missed since the alignment scores are likely to have low statistical significance. In conclusion, the results of such a strategy underscore the utility of large genomic databases for in silico systematic drug target identification in the post-genomic era.Publication Types of inter-atomic interactions at the MHC-peptide interface: identifying commonality from accumulated data.(2002-05-13) Adrian, P.E.; Rajaseger, G.; Mathura, V.S.; Sakharkar, M.K.; Kangueane, P.; BIOINFORMATICS CENTRE; BIOSCIENCE CENTREBACKGROUND: Quantitative information on the types of inter-atomic interactions at the MHC-peptide interface will provide insights to backbone/sidechain atom preference during binding. Qualitative descriptions of such interactions in each complex have been documented by protein crystallographers. However, no comprehensive report is available to account for the common types of inter-atomic interactions in a set of MHC-peptide complexes characterized by variation in MHC allele and peptide sequence. The available x-ray crystallography data for these complexes in the Protein Databank (PDB) provides an opportunity to identify the prevalent types of such interactions at the binding interface. RESULTS: We calculated the percentage distributions of four types of interactions at varying inter-atomic distances. The mean percentage distribution for these interactions and their standard deviation about the mean distribution is presented. The prevalence of SS and SB interactions at the MHC-peptide interface is shown in this study. SB is clearly dominant at an inter-atomic distance of 3A. CONCLUSION: The prevalently dominant SB interactions at the interface suggest the importance of peptide backbone conformation during MHC-peptide binding. Currently, available algorithms are developed for protein sidechain prediction upon fixed backbone template. This study shows the preference of backbone atoms in MHC-peptide binding and hence emphasizes the need for accurate peptide backbone prediction in quantitative MHC-peptide binding calculations.Publication Phylogenetic relationships of the seven coat protein subunits of the coatomer complex, and comparative sequence analysis of murine xenin and proxenin(2001) Chow, V.T.K.; Yeo, W.M.; Sakharkar, M.K.; Lim, D.P.P.; BIOINFORMATICS CENTRE; MICROBIOLOGYPublication Development of software tools at BioInformatics Centre (BIC) at the National University of Singapore (NUS).(1998) Kolatkar, P.R.; Sakharkar, M.K.; Tse, C.R.; Kiong, B.K.; Wong, L.; Tan, T.W.; Subbiah, S.; COMPUTER CENTRE; BIOINFORMATICS CENTRE; INFORMATION SYSTEMS & COMPUTER SCIENCEThere is burgeoning volume of information and data arising from the rapid research and unprecedented progress in molecular biology. This has been particularly affected by the Human Genome Project which is trying to completely sequence three billion nucleotides of the human genome (1),(1a). Other genome sequencing projects are also contributing substantially to this exponential growth in the number of DNA nucleotides and proteins sequenced. The number of journals, reports and research papers and tools required for the analysis of these sequences has also increased. For this the life sciences today needs tools in information technology and computation to prevent degeneration of this data into an inchoate accretion of unconnected facts and figures. The recently formed BioInformatics Centre (BIC) at the National University of Singapore (NUS) provides access to various commonly used computational tools available over the World Wide Web (WWW)--using a uniform interface and easy access. We have also come up with a new database tool. BioKleisli, which allows you to interact with various geographically scattered, heterogeneous, structurally complex and constantly evolving data sources. This paper summarises the importance of network access and database integration to biomedical research and gives a glimpse of current research conducted at BIC.Publication Human genomic diversity, viral genomics and proteomics, as exemplified by human papillomaviruses and H5N1 influenza viruses.(BioMed Central Ltd., 2009) Sakharkar M.K.; Sakharkar K.R.; Chow V.T.; MICROBIOLOGY AND IMMUNOLOGY; NATIONAL UNIVERSITY MEDICAL INSTITUTESPublication Generation of a database containing discordant intron positions in eukaryotic genes (MIDB)(2001) Sakharkar, M.K.; Tan, T.W.; De Souza, S.J.; BIOINFORMATICS CENTRE; BIOCHEMISTRYMotivation: Intron sliding is the relocation of intron-exon boundaries over short distances and is often also referred to as intron slippage or intron migration or intron drift. We have generated a database containing discordant intron positions in homologous genes (MIDB-Mismatched Intron DataBase). Discordant intron positions are those that are either closely located in homologous genes (within a window of 10 nucleotides) or an intron position that is present in one gene but not in any of its homologs. The MIDB database aims at systematically collecting information about mismatched introns in the genes from GenBank and organizing it into a form useful for understanding the genomics and dynamics of introns thereby helping understand the evolution of genes. Results: Intron displacement or sliding is critically important for explaining the present distribution of introns among orthologous and paralogous genes. MIDB allows examining of intron movements and allows mapping of intron positions from homologous proteins onto a single sequence. The database is of potential use for molecular biologists in general and for researchers who are interested in gene evolution and eukaryotic gene structure. Partial analysis of this database allowed us to identify a few putative cases of intron sliding.Publication Computational identification and experimental validation of PPRE motifs in NHE1 and MnSOD genes of human(BioMed Central Ltd., 2009) Gireedhar Venkatachalam; Kumar A.P.; Yue L.S.; Pervaiz S.; Clement M.V.; Sakharkar M.K.; PHYSIOLOGY; BIOINFORMATICS CENTRE; CANCER SCIENCE INSTITUTE OF SINGAPORE; BIOCHEMISTRYPublication TRES: Comparative promoter sequence analysis(2000) Katti, M.V.; Sakharkar, M.K.; Ranjekar, P.K.; Gupta, V.S.; BIOINFORMATICS CENTRESummary: Comparative promoter analysis is a promising strategy for elucidation of common regulatory modules conserved in evolutionarily related sequences or in genes showing common expression profiles. To facilitate such analysis, we have developed a software tool that detects conserved transcription factor binding sites, cis-elements, palindromes and k-tuples simultaneously in a set of sequences, and thus helps to identify putative motifs for designing further experiments.Publication ExInt: An Exon/Intron database(2000-01-01) Sakharkar, M.; Long, M.; Tan, T.W.; De Souza, S.J.; BIOINFORMATICS CENTRE; BIOCHEMISTRYThe Exon/Intron (ExInt) database incorporates information on the exon/intron structure of eukaryotic genes. Features in the database include: intron nucleotide sequence, amino acid sequence of the corresponding protein, position of the introns at the amino acid level and intron phase. From ExInt, we have also generated four additional databases each with ExInt entries containing predicted introns, introns experimentally defined, organelle introns or nuclear introns. ExInt is accessible through a retrieval system with pointers to GenBank. The database can be searched by keywords, locus name, NID, accession number or length of the protein. ExInt is freely accessible at http://intron.bic.nus.edu.sg/exint/exint.html.Publication A novel genomics approach for the identification of drug targets in pathogens, with special reference to Pseudomonas aeruginosa(2004) Sakharkar, K.R.; Sakharkar, M.K.; Chow, V.T.K.; BIOINFORMATICS CENTRE; MICROBIOLOGY