Papers by Sankaran Krishnaswamy
C-H center dot center dot center dot O hydrogen bonds in beta-sheets
A detailed analysis of the occurrence of the C-H ... O hydrogen bonds in sheet regions of protein... more A detailed analysis of the occurrence of the C-H ... O hydrogen bonds in sheet regions of proteins has been presented. 11 unique protein structures with resolution 1.3 Angstrom containing beta-sheets show a widespread presence of C-H .... O hydrogen bonds. These have average C-alpha... O, CH ... O distances and a C-alpha-H ... O angle of 3.29, 2.38 Angstrom and 143 degrees, respectively. As in the case of N-H ... O hydrogen bonds, parallel and antiparallel beta-sheet regions show the same hydrogen-bonds geometry. An inverse correlation is observed between the hydrogen-bond geometries involving the C-i(alpha)-H ... O=C and the Ni+1-H ... O=C suggesting that C-H ... O hydrogen bonds may act as an additional stabilizing factor. The propensity of different aminoacid residues to form such hydrogen bonds varies and shows a clear preference for valine and threonine. C-H ... O hydrogen bonds involving side chains also occur extensively in beta-sheet regions.
Molecular Diversity, 2021
The SARS-CoV-2 helicase Nsp13 is a promising target for developing anti-COVID drugs. In the prese... more The SARS-CoV-2 helicase Nsp13 is a promising target for developing anti-COVID drugs. In the present study, we have identified potential natural product inhibitors of SARS-CoV-2 Nsp13 targeting the ATP-binding site using molecular docking and molecular dynamics (MD) simulations. MD simulation of the prepared crystal structure of SARS-CoV-2 Nsp13 was performed to generate an ensemble of structures of helicase Nsp13 capturing the conformational diversity of the ATP-binding site. A natural product library of more than 14,000 phytochemicals from Indian medicinal plants was used to perform virtual screening against the ensemble of Nsp13 structures. Subsequently, a two-stage filter, first based on protein-ligand docking binding energy value and second based on protein residues in the ligand-binding site and non-covalent interactions between the protein residues and the ligand in the best-docked pose, was used to identify 368 phytochemicals as potential inhibitors of SARS-CoV-2 helicase Nsp13. MD simulations of the top inhibitors complexed with protein were performed to confirm stable binding, and to compute MM-PBSA based binding energy. From among the 368 potential phytochemical inhibitors, the top identified potential inhibitors of SARS-CoV-2 helicase Nsp13 namely, Picrasidine M, (+)-Epiexcelsin, Isorhoeadine, Euphorbetin and Picrasidine N, can be taken up initially for experimental studies.
The Journal of Membrane Biology, 2019
The membrane-active protein Nogo-66 is found to induce interdigitation in dimyristoylphosphocholi... more The membrane-active protein Nogo-66 is found to induce interdigitation in dimyristoylphosphocholine membranes. Extensive molecular dynamics simulations have been employed to probe the interactions of Nogo-66 with these model membranes. This phase change happens when the temperature is close to the main transition temperature of the membrane (T m) and only in the presence of the protein. No similar interdigitation of the membrane lipids was observed temperatures well above T m in the presence of the protein. In addition, in protein-free simulations, no interdigitation of the membrane lipids was found both at temperatures near or well above T m indicating that the observed effect is caused by the interactions of Nogo-66 with the membrane. Analysis of the simulations suggest protein-membrane interactions, even if transient, alter the lifetimes of lipid head defects and can potentially alter the effective T m and cause interdigitation. This study emphasize the importance of membrane-active proteins and their interactions with membranes leading to phase transitions which would affect other membrane-related processes such as domain formation.
Current Science, 2016
The spread of bioinformatics centres across India is primarily due to the extensive infrastructur... more The spread of bioinformatics centres across India is primarily due to the extensive infrastructure and network that was initiated way back in 1980s by S. Ramachandran, the first Secretary of the Department of Biotechnology (DBT), Government of India, and is being supported at 168 locations across the country. Anticipating the dawn of bioinformatics globally as an integration of informatics and biology, the seeds were sown by the linkage set up by the National Informatics Centre (NIC) led by N. Seshagiri (Director General of NIC), in a remarkable collaboration with DBT. As with biotechnology, strong teaching initiatives by DBT at the postgraduate level across the country helped in the growth. The recent bioinformatics certification examinations and the consequent fellowships are part of a seminal exercise that tries to provide standards in an area which saw unregulated mushrooming growth in the last decade. Unlike in the USA and Europe, where bioinformatics was nucleated by sequence analysis, in India the strong crystallography and biophysics structural background from the tradition of G. N. Ramachandran resulted in the initial tilt of bioinformatics in India towards structural perspectives. The Biotechnology Information System Network (BTISNET) captured through development of databases, by the centres distributed across the country, recording the diversity of biological resources in the country. The advent of mega sequencing and the large-scale import of genomics and proteomics technologies resulted in the growth of many bioinformatics groups and companies, several of which have connections to the centres of the BTISNET. Following the bioinformatics policy document, the recent years have seen the nurturing of the North Eastern Bioinformatics Network and also international collaborative ventures with countries in Asia and Europe. The trend of an admixture of experimental and computational biology approaches that are needed for systems and synthetic biology is becoming common and signals the next phase of expansion and integration of the bioinformatics network.
Genome Biology, 2005
Background Numerous completely sequenced bacterial genomes harbor prophage elements. These eleme... more Background Numerous completely sequenced bacterial genomes harbor prophage elements. These elements have been implicated in increasing the virulence of the host and in phage immunity. The e14 element is a defective lambdoid prophage element present at 25 min in the Escherichia coli K-12 genome. e14 is a well-characterized prophage element and has been subjected to in-depth bioinformatic analysis. Results A protein-based comparative
Intelligent Control and Automation
Prophages are integrated viral genomes in bacteria. Prophages are distinct from other genomic seg... more Prophages are integrated viral genomes in bacteria. Prophages are distinct from other genomic segments encoding virulence factors that have been acquired by horizontal gene transfer events. A database for prophages (http://bicmku.in:8082/prophagedb http://ispc.weizmann.ac.il/prophagedb) has been constructed with data available from literature reports. To date other than bacteriophage corner stone genes based iterative searches, no other exhaustive approach unique for identifying prophage elements is available. Here we report detection of prophages based on proteomic signature comparison using a prophage proteome as reference set. This method was tested with using the database and then extended over newly sequenced bacterial genomes with no reported prophages. The approach of using similarity of proteins over a given region helped identify twenty putative prophage regions in nine different bacterial genomes.
Archives of Biochemistry and Biophysics, 1983
Aptamer-based label-free detection of PDGF using ruthenium(II) complex as luminescent probe
Analytical and Bioanalytical Chemistry, 2013
We report a simple, cost-effective, and label-free detection method, consisting of a platelet-der... more We report a simple, cost-effective, and label-free detection method, consisting of a platelet-derived growth factor (PDGF) binding aptamer and hydrophobic Ru(II) complex as a sensor system for PDGF. The binding of PDGF with the aptamer results in the weakening of the aptamer-Ru(II) complex, monitored by luminescence signal. A substantial enhancement in the luminescence intensity of Ru(II) complex is observed in the presence of aptamer due to the hydrophobic interaction. Upon addition of PDGF, the luminescence intensity is decreased, due to the stronger interaction between the aptamer and PDGF resulting in the displacement of Ru(II) complex to the aqueous solution. Our assay can detect a target specifically in a complex medium such as the mixture of proteins, at a concentration of 0.8 pM.
Variation of prophage number with bacterial genomes
Prophage loci, in pathogenic bacteria, identified by the method reported here (DRAD approach) indicated as * are PAIs reported by Yoon <i>et al</i> 2005 [22]
The genetic functions of a generic lambdoid bacteriophage genome (brown rectangle) are shown above displayed with a transcriptional map (black arrows)
<b>Copyright information:</b>Taken from "Analysis of the lambdoid prophage eleme... more <b>Copyright information:</b>Taken from "Analysis of the lambdoid prophage element e14 in the K-12 genome"BMC Microbiology 2004;4():4-4.Published online 20 Jan 2004PMCID:PMC331406.Copyright © 2004 Mehta et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. In the middle, the section of the K-12 genome that contains e14 (gray rectangle) is shown with ORFs denoted by rectangular arrows oriented in the direction of transcription (green – host genes; red – e14 genes that are likely nonfunctional; black – e14 genes that are known to be functional; blue – e14 genes whose functionality cannot be assessed at present; parentheses indicate the boundaries of the P-invertable element). Small black arrows above the e14 map denote putative promoters, vertical lines denote putative terminators and small black squares putative operators. The yellow regions between the lambdoid and e14 maps indicate regions where e14 has homology to at least one known member of the lambdoid phage family (see text for details). Below, colored rectangles mark regions of highest homology between e14 and various known phages and prophages with regions of greater similarity closer to the e14 map (these are not meant to show all known homologies, only the closest ones); CPS-53 is a defective prophage in K-12, CP-933H is prophage in EDL933 and CP073-5, Sti4b, and Sti8 are provisional names for prophages in CFT073 and CT18 (Supplementary Material of Ref. []).
A simulation model of osmoregulatory switch using E-CELL system-1
<b>Copyright information:</b>Taken from "A simulation model of osmoregulatory sw... more <b>Copyright information:</b>Taken from "A simulation model of osmoregulatory switch using E-CELL system"BMC Microbiology 2004;4():44-44.Published online 30 Nov 2004PMCID:PMC543474.Copyright © 2004 Srividhya and Krishnaswamy; licensee BioMed Central Ltd.vZ is triggered to take up either kinase or phosphatase activity. In high osmolarity conditions the higher osmolyte medium (NB (Nutrient Broth)+20% sucrose) makes the kinase activity of EnvZ (EnvZk) predominate the phosphatase activity resulting in the formation of EnvZkpOmpR complex. Finally after the phosphotransfer of phosphate group to OmpR, the promoter sites of OmpF are occupied in cooperative manner with F1, F1F2 and F1F2F3, high affinity binding sites. The cellular concentration of OmpRP makes it available for the OmpC promoter C1, C1C2, C1C2C3. Additionally OmpRP binds to F4 after binding F1F2F3 promoter directly repressing OmpF expression, thereby facilitating OmpC expression.
Journal of biomolecular structure & dynamics, Jan 27, 2017
More than 60 prediction methods for intrinsically disordered proteins (IDPs) have been developed ... more More than 60 prediction methods for intrinsically disordered proteins (IDPs) have been developed over the years, many of which are accessible on the World Wide Web. Nearly, all of these predictors give balanced accuracies in the ~65%-~80% range. Since predictors are not perfect, further studies are required to uncover the role of amino acid residues in native IDP as compared to predicted IDP regions. In the present work, we make use of sequences of 100% predicted IDP regions, false positive disorder predictions, and experimentally determined IDP regions to distinguish the characteristics of native versus predicted IDP regions. A higher occurrence of asparagine is observed in sequences of native IDP regions but not in sequences of false positive predictions of IDP regions. The occurrences of certain combinations of amino acids at the pentapeptide level provide a distinguishing feature in the IDPs with respect to globular proteins. The distinguishing features presented in this paper p...
Proteins: Structure, Function, and Bioinformatics, 2017
Porins form trimers in the outer membrane and help transport nutrients and waste products across ... more Porins form trimers in the outer membrane and help transport nutrients and waste products across the bacterial cell membrane. Porin loops are suitable candidates as display systems due to their high immunogenicity and presentation at the bacterial cell surface. In this study, Salmonella typhi porins (OmpC and OmpF) engineered with the Kennedy peptide from gp41 of HIV were characterised. The chimeric OmpC carrying the Kennedy peptide in loop7 did not trimerise, whereas the chimeric OmpF with the epitope in loop5 formed trimers and also was recognised by the antibodies in the HIV patient serum. The results suggest that chimeric S. typhi OmpF may be taken further as a potential candidate to develop as an epitope display system.
Bioinformation, 2016
Molecular Pathways Brain Database (MPDB), is a novel database for molecular information of the br... more Molecular Pathways Brain Database (MPDB), is a novel database for molecular information of the brain pathways and is an initiative to provide an organized platform for researchers in the field of neuro-informatics. The database currently has information from 1850 molecules for three different sensory pathways namely olfactory transduction, photo transduction and long-term potentiation. The usefulness of the database is demonstrated by an analysis of the olfactory transduction pathway which helps understand their olfactory specifity and further indicates that some of the molecules have evolved independently among these organisms as per the need of time and function.
Crystal structure of YagE, a prophage protein belonging to the dihydrodipicolinic acid synthase family from E. coli K12 in complex with pyruvate
Crystal structure of YagE, a prophage protein from E. coli K12 in complex with KDGal
International Journal of Bioinformatics Research and Applications, 2015
O104:H4 is a new strain of E. coli that has caused an outbreak in Germany. It was isolated from p... more O104:H4 is a new strain of E. coli that has caused an outbreak in Germany. It was isolated from patients with bloody diarrhoea and Haemolytic Uremic Syndrome (HUS). BGI (www.genomics.cn) sequenced and assembled this new strain. It was reported to show resistance to a number of drugs that are toxic to other E. coli and causes serious complications during infections, which ultimately lead to death. Multi-drug resistance and high virulence of this strain is thought to be acquired from different sources, by horizontal gene transfer. A total of 38 prophage elements were detected from the new strain by using three computational tools viz., DRAD, Prophage Finder and PHAST. Analysis on these prophage elements shows a number of virulence proteins like Shiga toxin and multi-drug resistance protein encoding genes. The high virulence of the strain could be attributed by the prophage elements acquired from its micro environment.
Molecular vision, Jan 29, 2010
To examine the possible role of alternate splicing leading to aggregation of myocilin in primary ... more To examine the possible role of alternate splicing leading to aggregation of myocilin in primary open-angle glaucoma. Several single nucleotide variations found in the myocilin (MYOC) genomic region were collected and examined for their possible role in causing splice-site alterations. A model for myocilin built using a knowledge-based consensus method was used to map the altered protein products. A total of 150 open-angle glaucoma patients and 50 normal age-matched control subjects were screened for the predicted polymorphisms, and clustering was performed. A total of 124 genomic variations were screened, and six polymorphisms that lead to altered protein products were detected as possible candidates for the alternative splicing mechanism. Five of these lay in the intronic regions, and the one that lay in the exon region corresponded to the previously identified polymorphism (Tyr347Tyr) implicated in primary open-angle glaucoma. Experimentally screening the intronic region of the M...
Journal of Ocular Biology, Diseases, and Informatics, 2011
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Papers by Sankaran Krishnaswamy