Papers by Dr. Abhijit Datta
The pathogenesis of HIV-1 is complex and characterized by the interplay of both viral and hostfac... more The pathogenesis of HIV-1 is complex and characterized by the interplay of both viral and hostfactors. Within HIV 1 genome there are several snRNP motifs responsible for pre mRNA splicing andstabilization. By locating these motifs within the genome and disturbing them may result in an impairedability of the cells to sustain HIV-1 replication. One of such regulatory sequences is riboswitches thatregulate the dimerization of HIV-1 RNA, which is an essential step during packaging. The current workwas undertaken to identify possible regulatory RNA motifs in the HIV1 genome from different isolates.The current work has successfully identified multiple snRNP motifs in the genome sequences ofdifferent strains of HIV-1 isolates. The identification of the multiple snRNP motifs in the genomicsequences of the various isolates lead us to believe that future studies with artificially constructedsnRNPs might have the potential to inhibit HIV1 replication. Apart from containing snRNP motifs theyals...
Toxicon, 2019
Cholera is a major global threat, affecting millions each year. The ADP ribosyltransferase activi... more Cholera is a major global threat, affecting millions each year. The ADP ribosyltransferase activity of the active cholera toxin catalyses the massive loss of water and electrolytes during cholera infections. The active toxin heterodimer comprises the A1 subunit from Vibrio cholerae and ARF (ADP Ribosylation Factor) from the human host. Although the active toxin is a potential target for drug discovery against cholera, it has been scarcely targeted to date. The A1-ARF interface contains a potential druggable site for small molecule inhibitors. By combining a sequential docking and scoring strategy with molecular dynamics (MD) simulations, this study identified hits against the protein-protein interface (PPI) of the active cholera toxin from an in-house library of 9,175 ADMET-screened alkaloids. The docking algorithms and scoring functions of Glide SP, Glide XP, and AutoDock were employed for initial library screening. Three alkaloids were initially selected by docking-based virtual screening. The stability of the hit-toxin complexes was validated by MD simulations. Two of the three hits, namely, A6225 (7-formyldehydrothalicsimidine) and A16503 (1,2,7,8-tetrahydroxy dibenz[cd,f]indol-4(5H)-one), formed stable complexes with the toxin. Analyses of the hydrogen bond occupancies revealed that the hits formed stable hydrogen bonds with the toxin PPI. The hits identified herein can serve as reference compounds for drug discovery against cholera in the future.
Scientific Reports, 2019
Lantibiotics are lanthionine-containing bactericidal peptides produced by gram-positive bacteria ... more Lantibiotics are lanthionine-containing bactericidal peptides produced by gram-positive bacteria as a defence mechanism against other bacterial species. Lantipeptides disrupt the integrity of target cells by forming pores in their cell membranes, or by preventing cell wall biosynthesis, which subsequently results in cell death. Lantibiotics are of immense importance to the food preservation and pharmaceutical industries. the rise in multidrug resistance demands the discovery of novel antimicrobials, and several authors advocate that lantibiotics hold the future of antimicrobial drug discovery. Owing to their amenability to structural modifications, novel lantibiotics with higher efficacy and antimicrobial activity can be constructed by bioengineering and nanoengineering strategies, and is opined to have immense therapeutic success in combating the rise in multidrug resistance. Understanding the structure and dynamics of lantibiotics is therefore crucial for the development of novel lantipeptides, and this study aimed to study the structural properties and dynamics of 37 lantibiotics using computational strategies. The structures of these 37 lantibiotics were constructed from homology, and their structural stability and compactness were analysed by molecular dynamics simulations. the phylogenetic relationships, physicochemical properties, disordered regions, pockets, intramolecular bonds and interactions, and structural diversity of the 37 lantipeptides were studied. The structures of the 37 lantipeptides constructed herein remained stable throughout simulation. The study revealed that the structural diversity of lantibiotics is not significantly correlated to sequence diversity, and this property could be exploited for designing novel lantipeptides with higher efficacy. Lantibiotics are ribosomally-synthesised peptide bacteriocins, produced by gram-positive bacteria for targeting other bacterial species during defence strategies, and undergo extensive post-translational modifications prior to forming the mature functional lantipeptide 1,2. Lantibiotics, or lanthionine-containing antibiotics, are so named because they contain unusual amino acids, lanthionine (Lan) and methyllanthionine (MeLan), which are formed by the fusion of two alanines cross-linked by a thioether linkage 1,3. Lantipeptides also contain several unsaturated amino acids, including dehydroalanine and dehydrobutyrine 1. The bacteriocidal activity of lantibiotics is attributed to the formation of stable pores in the target membrane, which disrupts cellular integrity or prevents cell wall biosynthesis 4-6. Lantipeptides are highly sought after antimicrobials in the food preservation and pharmaceutical industries owing to their low toxicity in mammalian systems, higher potency than antibiotics, few or no reports of lantibiotic resistance in bacteria, and potent activity against drug-resistant strains such as MRSA and VRE 7-11. Drug resistance is a serious global concern at present, and the rising emergence of resistant strains demands the design of novel therapeutic strategies. Antibiotic resistant strains often develop biofilms, which further aggravates the crisis of resistance, necessitating the prevention of biofilm formation. The potential of several lantibiotics including nisin, nukacin ISK-1, and gallidermin in hindering the formation of biofilms in staphylococcal strains such as MRSA is widely known 12. Numerous studies have demonstrated the efficacy of lantibiotics against resistant strains including MRSA, VRE, and GISA 13,14. Several authors emphasise on the potential of lantibiotics in combating the emerging drug resistant strains and support
The accurate prediction of a comprehensive set of messenger putative antagomirs against microRNAs... more The accurate prediction of a comprehensive set of messenger putative antagomirs against microRNAs (miRNAs) remains an open problem. In particular, a set of putative antagomirs against human miRNA is predicted in this current version of database. We have developed Antagomir database, based on putative antagomirs-miRNA heterodimers. In this work, the human miRNA dataset was used as template to design putative antagomirs, using GC content and secondary structures as parameters. The algorithm used predicted the free energy of unbound antagomirs. Although in its infancy the development of antagomirs, that can target cell specific genes or families of genes, may pave the way forward for the generation of a new class of therapeutics, to treat complex inflammatory diseases. Future versions need to incorporate further sequences from other mammalian homologues for designing of antagomirs for aid in research. Availability:
Bacterial peptides of low molecular weight displaying antagonism towards other bacterialmembers a... more Bacterial peptides of low molecular weight displaying antagonism towards other bacterialmembers are referred to as bacteriocins. Bacteriocins are an essential member of the broadly classifiedgroup of lantibiotics which finds several commercial uses. This work comprises of the determination ofstructure of the most important class of bacteriocins – the leucocin group. Structure elucidation wasperformed using homology modelling approach and the modeled structure was validated using theirRamachandran calculations. Ligand interaction pockets were identified by calculating the Delaunaytriangulation number and structural properties of amino acids were documented. Structure elucidations ofsuch lantibiotics are important for future endeavours towards analyses of protein - protein interactions.
International Letters of Natural Sciences, 2015
RNA silencing is one of the important phenomenon in plant defense mechanism, it actively protect ... more RNA silencing is one of the important phenomenon in plant defense mechanism, it actively protect host plants against viral infections. Existing viruses must have developed counter defense strategies to survive this arms race. Such counter defense strategy is the viral silencing suppressor (VSRs) which have been reported to directly interfere with the various steps leading to the interference of viral RNAs. Most identified VSRs are multifunctional, besides being RNA-silencing suppressors, they often perform essential roles by functioning as coat proteins, helper components for viral transmission, replicases and movement proteins, proteases or transcriptional regulators. One such identified VSR is AC4 of Sri Lankan cassava mosaic virus strain. Trivial knowledge about the structure –function relationship of this VSR leads to this work, where we focus on the structure generation by modelling to identify the mode of interactions with the various effector molecules of the silencing pathwa...
International Letters of Natural Sciences, 2014
Incomplete reduction of oxygen molecules is the primary source for the formation of reactive oxyg... more Incomplete reduction of oxygen molecules is the primary source for the formation of reactive oxygen species (ROS) during cytosolic metabolism or mitochondrial respiration. These phenomenons may be as a result of biotic or abiotic stress. Exposure to exogenous stimuli such as radiation might be an alternative pathway of ROS production. Thus plants require counter defense strategies to combat the increase of this toxic molecular build up in its cell cytoplasm. As a result they have devised an army of free radical scavenging enzymes which enable them to dissipate the oxidative stress imposed by the accumulation of these toxic moieties. Glutathione Peroxidase forms an important part of this arms race along with several catalases and organelle specific enzymes such as superoxide dismutase. Plant glutathione peroxidases (GPXs) have been studied exclusively for their evolutionary lineages since they represent a hybrid class of molecules in context of the presence and absence of selenocyste...
BMC Bioinformatics, 2010
This article has been withdrawn from the public domain because of significant plagiarism. In the ... more This article has been withdrawn from the public domain because of significant plagiarism. In the light of this situation, BioMed Central regrets that this article is no longer available. The authors apologise to all affected parties for the inconvenience.
Biotechnology, 2019
Protein docking is integral to structure-based drug design and molecular biology. The recent surg... more Protein docking is integral to structure-based drug design and molecular biology. The recent surge of big data in biology, the demand for personalised medicines, evolving pathogens and increasing lifestyle-associated risks, asks for smart, robust, low-cost and high-throughput drug design. Computer-aided drug design techniques allow rapid screening of ultra-large chemical libraries within minutes. This is immensely necessary to the drug discovery pipeline, which is presently burdened with high attrition rates, failures, huge capital and time investment. With increasing drug resistance and difficult druggable targets, there is a growing need for novel drug scaffolds which is partly satisfied by fragment based drug design and de novo methods. The chapter discusses various aspects of protein docking and emphasises on its application in drug design.
Advances in Bioinformatics and Biomedical Engineering, 2018
The great disagreement between the number of known protein sequences and the number of experiment... more The great disagreement between the number of known protein sequences and the number of experimentally determined protein structures indicate an enormous necessity of rapid and accurate protein structure prediction methods. Computational techniques such as comparative modeling, threading and ab initio modelling allow swift protein structure prediction with sufficient accuracy. The three phases of computational protein structure prediction comprise: the pre-modelling analysis phase, model construction and post-modelling refinement. Protein modelling is primarily comparative or ab initio. Comparative or template-based methods such as homology and threading-based modelling require structural templates for constructing the structure of a target sequence. The ab initio is a template-free modelling approach which proceeds by satisfying various physics-based and knowledge-based parameters. The chapter will elaborate on the three phases of modelling, the programs available for performing eac...
International journal of bioinformatics research, Apr 20, 2011
Snurps or small nuclear ribonucleoproteins (snRNPs), are RNA-protein complexes that combine with ... more Snurps or small nuclear ribonucleoproteins (snRNPs), are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a Spliceosome, comprising of five small nuclear RNAs (snRNAs)-U1, U2, U4, U5, and U6 snRNA-as well as many protein factors, upon which splicing of pre-mRNA occurs. While, RNA pseudoknots play crucial role in protein synthesis by helping in internal ribosome entry, frameshifting, stop codon readthrough in many viral species and the 3'NCR pseudoknots helps viral RNAs to replicate, has been reported by a number of investigators, its presence in human snurps has not yet been done. The present in silico study reveals the presence of pseudoknots in the mRNAs of the proteins associated with human Spliceosome. It not only emphasizes their significance as catalytic RNA world relics but also opens the scope of research in the functional and structural associations of RNA pseudoknots in eukaryotic gene regulation.
Abstract--The Gene Expression Omnibus (GEO) maintained at the National Center for Biotechnology I... more Abstract--The Gene Expression Omnibus (GEO) maintained at the National Center for Biotechnology Information (NCBI) is an archive where microarray data is available freely to researchers. The database provides us with numerous data deposit options including web forms, spreadsheets, XML and Simple Omnibus Format in Text (SOFT). Along with the purpose of a repository a large collection of tools are available to help users effectively explore, and analyze gene expression patterns stored in GEO. The need for better analyses of gene expression data was explored using object oriented programming languages such as C and Practical extraction and reporting language (PERL). The test set that was used for this study were human transcription factors. The results obtained indicate that feature extraction was successful.
Trends in Bioinformatics, 2018
Protein kinase CK2 is a critical regulator of several cellular and molecular signaling pathways. ... more Protein kinase CK2 is a critical regulator of several cellular and molecular signaling pathways. CK2 is unanimously distributed in eukaryotes and subsists in tetrameric complexes comprising two catalytic alpha and two regulatory beta subunits. Several reports have confirmed that protein kinase CK2 has great significance in diverse biological courses, particularly in cellular growth and proliferation in normal and disease conditions. However, in silico analysis of phosphorylation sites in the catalytic alpha subunit of CK2 remains to be elucidated. We described the distribution of predicted (neural network predictions for serine (S), threonine (T) and tyrosine(Y)) STY phosphorylation sites in CK2 alpha subunit of 15 multicellular and 2 unicellular organisms. We also showed the clustering of CK2 alpha subunit in these organisms using a phylogram. This data showed the prevalence of CK2 alpha subunits with potential STY phophorylation sites in several eukaryotic unicellular and mulicellular organisms that could be significant in the context of enigmatic protein kinase activities of CK2, enzyme-substrate interactions, further ligand-binding studies and new therapeutic interventions.
Food Research International, 2015
Abstract Glycation is known to be related with several pathophysiological complications. Several ... more Abstract Glycation is known to be related with several pathophysiological complications. Several chemical and natural compounds had been tested on different systems to prevent glycation-related complications. Though they show a promising result initially, but often fail to succeed in preclinical trials. In this paper, we try to demonstrate how syringic and chlorogenic acids, two largely consumed natural products bind with BSA to prevent glycation-associated complications. Biochemical (glucose estimation) and biophysical (CD, MALDI, MS/MS) techniques have been used to demonstrate the antiglycating mechanism. We have calculated binding constant 3.07 ± 0.42 × 10− 4 and 2.67 ± 0.28 × 10− 4 M− 1 for syringic and chlorogenic acids respectively. Further we have successfully purified BSA–phenolic acid conjugates by chromatographic methods. Molecular modeling and mass spectrometric studies suggested that Lys 93,261,232, Arg 194 and Lys 93, Arg 194 are the responsible binding residues for syringic and chlorogenic acids respectively.
International Letters of Natural Sciences, 2013
Plant glutathione peroxidases are an important class of enzymes which play key roles in the stres... more Plant glutathione peroxidases are an important class of enzymes which play key roles in the stress adaptability of plants both in context of biotic and abiotic stress pathways. They have been over the years much studied in animals since the catalytic residues are comprised of selenocysteine a variant amino acid which is ribosomally encoded with the help of an RNA structural element known as SECIS. Various workers over the years have shown that plant glutathione peroxidases play active roles in ROS sequestration, lipid hydroperoxidation as well as regulate glutathione levels. However, each plant has various patterns of glutathione peroxidase expression and action and in some plants certain isoforms have not been detected at all. This work focuses on the prediction and identification of single nucleotide polymorphisms (SNPs) and INDELs in the coding regions of plant glutathione peroxidases, with the help of a Bayesian based algorithm subsequently validated. A large number of informati...
International Journal of Bioinformatics Research, 2009
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Papers by Dr. Abhijit Datta