Shishir Gupta

Publications

• 2.34

  Impact points

  Structure prediction and binding sites analysis of curcin protein of Jatropha curcas using computational approaches.

  Mugdha Srivastava, Shishir K Gupta, P C Abhilash, Nandita Singh

  Journal of molecular modeling. 12/2011;

  Ribosome inactivating proteins (RIPs) are defense proteins in a number of higher-plant species that are directly targeted toward herbivores. Jatropha curcas is one of the biodiesel plants having RIPs. The Jatropha seed meal, after extraction of oil, is rich in curcin, a highly toxic RIP similar to r... [more] Ribosome inactivating proteins (RIPs) are defense proteins in a number of higher-plant species that are directly targeted toward herbivores. Jatropha curcas is one of the biodiesel plants having RIPs. The Jatropha seed meal, after extraction of oil, is rich in curcin, a highly toxic RIP similar to ricin, which makes it unsuitable for animal feed. Although the toxicity of curcin is well documented in the literature, the detailed toxic properties and the 3D structure of curcin has not been determined by X-ray crystallography, NMR spectroscopy or any in silico techniques to date. In this pursuit, the structure of curcin was modeled by a composite approach of 3D structure prediction using threading and ab initio modeling. Assessment of model quality was assessed by methods which include Ramachandran plot analysis and Qmean score estimation. Further, we applied the protein-ligand docking approach to identify the r-RNA binding residue of curcin. The present work provides the first structural insight into the binding mode of r-RNA adenine to the curcin protein and forms the basis for designing future inhibitors of curcin. Cloning of a future peptide inhibitor within J. curcas can produce non-toxic varieties of J. curcas, which would make the seed-cake suitable as animal feed without curcin detoxification.
• 3.22

  Impact points

  Computational analysis and modeling the effectiveness of 'Zanamivir' targeting neuraminidase protein in pandemic H1N1 strains.

  Shailendra K Gupta, Shishir K Gupta, Suchi Smita, Mugdha Srivastava, Xin Lai, Ulf Schmitz, Qamar Rahman, Olaf Wolkenhauer, Julio Vera

  Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 04/2011; 11(5):1072-82.

  Antigenic drift causes number of mutations in neuraminidase protein of H1N1 swine influenza virus. We analyzed neuraminidase mutations in H1N1 strains distributed over six continents, at both the sequence and structural level. Mutations in the nearby residues of the drug binding site play crucial ro... [more] Antigenic drift causes number of mutations in neuraminidase protein of H1N1 swine influenza virus. We analyzed neuraminidase mutations in H1N1 strains distributed over six continents, at both the sequence and structural level. Mutations in the nearby residues of the drug binding site play crucial role in the binding affinity of the drug with the protein. For this purpose, mutant models were generated for the neuraminidase protein from 34 pandemic H1N1 isolates and docking were performed with zanamivir drug. Multiple sequence alignment (MSA) and variations in docking score suggest that there are considerable changes in the binding affinity of neuraminidase with zanamivir, which leads to probable ineffectiveness of zanamivir in the isolated samples of pandemic H1N1 collected from quite a few countries. To further evaluate the effectiveness of the antiviral drugs, we derived, calibrated and analyzed an ordinary differential equations based mathematical model for H1N1 infection dynamics and drug mediated virus deactivation.
• 1.59

  Impact points

  Interaction of C60 fullerene with the proteins involved in DNA mismatch repair pathway.

  Shishir Kumar Gupta, Lokesh Baweja, Deepak Gurbani, Alok K Pandey, Alok Dhawan

  Journal of biomedical nanotechnology. 02/2011; 7(1):179-80.

  Fullerenes are fascinating symmetric carbon nanostructures with a potential to bind DNA and proteins. Computational studies were performed to investigate the interaction of fullerenes with the proteins involved in DNA mismatch repair (MMR) pathway. Significant interactions of fullerene with PMS2, RF... [more] Fullerenes are fascinating symmetric carbon nanostructures with a potential to bind DNA and proteins. Computational studies were performed to investigate the interaction of fullerenes with the proteins involved in DNA mismatch repair (MMR) pathway. Significant interactions of fullerene with PMS2, RFC3 and PCNA proteins were observed. These findings suggested that fullerene interferes in the human MMR process hence the subsequent disturbance may confer a large increase in spontaneous mutability and a strong predisposition to tumor development.
• 2.32

  Impact points

  In silico identification of novel protective VSG antigens expressed by Trypanosoma brucei and an effort for designing a highly immunogenic DNA vaccine using IL-12 as adjuvant.

  Bashir Akhlaq Akhoon, Parvez Singh Slathia, Preeti Sharma, Shishir Kumar Gupta, Vijeshwar Verma

  Microbial pathogenesis. 02/2011; 51(1-2):77-87.

  African trypanosomiasis continues to be a major health problem, with more adults dying from this disease world-wide. As the sequence diversity of Trypanosoma brucei is extreme, with VSGs having 15-25% identity with most other VSGs, hence it displays a huge diversity of adaptations and host specifici... [more] African trypanosomiasis continues to be a major health problem, with more adults dying from this disease world-wide. As the sequence diversity of Trypanosoma brucei is extreme, with VSGs having 15-25% identity with most other VSGs, hence it displays a huge diversity of adaptations and host specificities. Therefore the need for an improved vaccine has become an international priority. The highly conserved and specific epitopes acting as both CD8+ and CD4+ T-cell epitopes (FLINKKPAL and FTALCTLAA) were predicted from large bunch of VSGs of T. brucei. Besides, some other potential epitopes with very high affinity for MHC I and II molecules were also determined while taking consideration on the most common HLA in the general population which accounts for major ethnicities. The vaccine candidates were found to be effective even for non-african populations as predicted by population coverage analysis. Hence the migrating travelers acting as a spread means of the infection can probably also be treated successfully after injection of such a multiepitopic vaccine. Exploiting the immunoinformatics approaches, we designed a potential vaccine by using the consensus epitopic sequence of 388 VSG proteins of T. brucei and performed in silico cloning of multiepitopic antigenic DNA sequence in pBI-CMV1 vector. Moreover, various techniques like codon adaptation, CpG optimization, removal of self recognized epitopes, use of adjuvant and co-injection with plasmids expressing immune-stimulatory molecules were implemented to enhance the immunogenicity of the proposed in silico vaccine.
• 3.88

  Impact points

  In silico proteomic characterization of human epidermal growth factor receptor 2 (HER-2) for the mapping of high affinity antigenic determinants against breast cancer.

  Urvashi Baloria, Bashir Akhlaq Akhoon, Shishir Kumar Gupta, Sujata Sharma, Vijeshwar Verma

  Amino acids. 01/2011; 42(4):1349-60.

  Multiple different approaches are being used to activate the immune system against breast cancer. Vaccine therapy in general follows the principle that injections of various substances ultimately result in the presentation of tumor peptides to the patient's immune system. We proposed a potential... [more] Multiple different approaches are being used to activate the immune system against breast cancer. Vaccine therapy in general follows the principle that injections of various substances ultimately result in the presentation of tumor peptides to the patient's immune system. We proposed a potential in silico DNA vaccine against breast cancer by integrating high affinity T cell (MHC-I and MHC-II) and B cell (continuous and discontinuous) epitopes. The matching of the HLA haplotype and antigen was performed to provide the appropriate peptide epitope suitable for majority of the patients. The immunogenic nature of the antigenic construct was also enhanced by the administration of consensus epitopes. The potency of DNA vaccines depends on the efficient expression and presentation of the encoded antigen of interest and the chances of efficient expression of our antigenic construct in host organism was also verified by in silico approaches. An attempt was made to overcome the limited potency of the DNA vaccine by targeting DNA to professional antigen-presenting cells (APCs). A higher immune response theoretically corresponds to a higher survival rate of patients. Therefore, optimization studies were also employed to enhance the immunogenicity of proposed in silico DNA vaccine.
• 3.22

  Impact points

  Identification of immunogenic consensus T-cell epitopes in globally distributed influenza-A H1N1 neuraminidase.

  Shishir K Gupta, Mugdha Srivastava, Bashir A Akhoon, Suchi Smita, Ulf Schmitz, Olaf Wolkenhauer, Julio Vera, Shailendra K Gupta

  Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 11/2010; 11(2):308-19.

  Antigenic drift is the ability of the swine influenza virus to undergo continuous and progressive changes in response to the host immune system. These changes dictate influenza vaccine updates annually to ensure inclusion of antigens of the most current strains. The identification of those peptides ... [more] Antigenic drift is the ability of the swine influenza virus to undergo continuous and progressive changes in response to the host immune system. These changes dictate influenza vaccine updates annually to ensure inclusion of antigens of the most current strains. The identification of those peptides that stimulate T-cell responses, termed T-cell epitopes, is essential for the development of successful vaccines. In this study, the highly conserved and specific epitopes from neuraminidase of globally distributed H1N1 strains were predicted so that these potential vaccine candidates may escape with antigenic drift. A total of nine novel CD8(+) T-cell epitopes for MHC class-I and eight novel CD4(+) T-cell epitopes for MHC class-II alleles were proposed as novel epitope based vaccine candidates. Additionally, the epitope FSYKYGNGV was identified as a highly conserved, immunogenic and potential vaccine candidate, capable for generating both CD8(+) and CD4(+) responses.
• 3.62

  Impact points

  In silico CD4+ T-cell epitope prediction and HLA distribution analysis for the potential proteins of Neisseria meningitidis Serogroup B--a clue for vaccine development.

  Shishir K Gupta, Suchi Smita, Aditya Narayan Sarangi, Mugdha Srivastava, Bashir A Akhoon, Qamar Rahman, Shailendra K Gupta

  Vaccine. 10/2010; 28(43):7092-7.

  Neisseria meningitidis, an exclusive human pathogen, is a major cause of mortality due to meningococcal meningitis and sepsis in many developing countries. Three meningococcal serogroup B proteins, i.e. T-cell stimulating protein A (TspA), autotransporter A (AutA), and IgA-specific serine endopeptid... [more] Neisseria meningitidis, an exclusive human pathogen, is a major cause of mortality due to meningococcal meningitis and sepsis in many developing countries. Three meningococcal serogroup B proteins, i.e. T-cell stimulating protein A (TspA), autotransporter A (AutA), and IgA-specific serine endopeptidase (IGA1) elicits CD4+ T-cell response and may enhance the effectiveness of meningococcal vaccines by acting as protective immunogens. A very limited data on T-helper cell epitopes in MenB proteins is available. Hence, in silico prediction of peptide sequences which may act as helper T lymphocyte epitopes in MenB proteins was carried out by NetMHCIIpan web server. HLA distribution analysis was done by using the population coverage tool of Immune Epitope Database to determine the fraction of individuals in various populations expected to respond to a given set of predicted T-cell epitopes based on HLA genotype frequencies. Six epitopic core sequences, two from each MenB proteins, i.e. AutA, TspA and IgA1 protease were predicted to associate with a large number of HLA-DR alleles. These six peptides may act as T-cell epitope in more than 95% of populations in 8 out of 12 populations considered. The T-cell stimulation potential of these predicted peptides containing the core epitopic sequences is to be validated by using laboratory experiments for their efficient use as peptide vaccine candidates against N. meningitidis serogroup B.
• 2.96

  Impact points

  Development of resistance against blackleg disease in Brassica oleracea var. botrytis through in silico methods.

  Mugdha Srivastava, Bashir A Akhoon, Shishir Kumar Gupta, Shailendra K Gupta

  Fungal genetics and biology : FG & B. 10/2010; 47(10):800-8.

  Blackleg caused by Leptosphaeria maculans is a very important disease worldwide and causes large yield loss of significant vegetable crops of Brassicaceae family. Absence of resistant 'B' genome in vegetable Brassica oleracea proposed these species susceptible to blackleg disease. We present... [more] Blackleg caused by Leptosphaeria maculans is a very important disease worldwide and causes large yield loss of significant vegetable crops of Brassicaceae family. Absence of resistant 'B' genome in vegetable Brassica oleracea proposed these species susceptible to blackleg disease. We present a specific piece of molecular modelling work, combining in silico docking methods, energy minimization calculations and in silico cloning, to develop a rational peptide as a candidate that functions as a resistance inducing agent against L. maculans in B. oleracea var. botrytis. These studies are based upon predicted interaction sites of isocitrate lyase (ICL) and isocitrate. Inhibition of isocitrate binding to ICL is demonstrated to prevent rescue of glyoxylate cycle that is essential for metabolism of L. maculans in B. oleracea. We have taken the predicted interaction domain from the isocitrate lyase enzyme and randomly generated the best fitting 9-amino acid peptide among various screened peptides.
• 2.34

  Impact points

  Virtual screening of specific chemical compounds by exploring E.coli NAD+-dependent DNA ligase as a target for antibacterial drug discovery.

  Bashir Akhlaq Akhoon, Shishir K Gupta, Gagan Dhaliwal, Mugdha Srivastava, Shailendra K Gupta

  Journal of molecular modeling. 05/2010; 17(2):265-73.

  Unique substrate specificity compared with ATP-dependent human DNA ligases recommends E.coli NAD(+)-ligases as potential targets. A plausible strategy is to identify the structural components of bacterial DNA ligase that interact with NAD(+) and then to isolate small molecules that recognize these c... [more] Unique substrate specificity compared with ATP-dependent human DNA ligases recommends E.coli NAD(+)-ligases as potential targets. A plausible strategy is to identify the structural components of bacterial DNA ligase that interact with NAD(+) and then to isolate small molecules that recognize these components and thereby block the binding of NAD(+) to the ligase. This work describes a molecular modeling approach to detect the 3D structure of NAD(+)-dependent DNA ligase in E. coli whose partial structure was determined by wet lab experiments and rest structure was left as such on the road for repairment. We applied protein-drug docking approach to detect the binding affinity of this enzyme with Quinacrine and some of its virtual derivatives. In silico docking results predict that the virtual derivative of Quinacrine (C21H26ClN3O2) has greater binding affinity than Quinacrine. Drug likeness value of 0.833 was observed for this derivative without showing any toxicity risk.

• A Novel Algorithm to Design an Efficient siRNA by Combining the Pre Proposed Rules of siRNA Designing

  Shishir Kumar Gupta, Bashir Akhlaq Akhoon, Srivastava Mugdha, Shailendra Kumar Gupta

  Journal of Computer Science & Systems Biology. 01/2010;

  Short interfering RNAs (siRNAs) can be used to suppressgene expression and have a lot of potential applications intherapy, yet how to design an effective siRNA is still underconsideration. Numerous siRNA design tools have beendeveloped recently. The set of candidates reported by thesetools is usuall... [more] Short interfering RNAs (siRNAs) can be used to suppressgene expression and have a lot of potential applications intherapy, yet how to design an effective siRNA is still underconsideration. Numerous siRNA design tools have beendeveloped recently. The set of candidates reported by thesetools is usually large and often contains ineffective siRNAs.We initiated with the filtering of ineffective siRNAs, specifically,the current work establishes relationship betweenmentioned theoretically calculated property of subsequencesand their efficiency for RNAi for any input set of experimentaldata. We combined some reported algorithms anddesigned a new algorithm that mainly focuses on stabilityand off-targeting to design siRNA sequences.
• 2.17

  Impact points

  In silico designing and optimization of anti-breast cancer antibody mimetic oligopeptide targeting HER-2 in women.

  Bashir A Akhoon, Shishir K Gupta, Vijeshwar Verma, Gagan Dhaliwal, Mugdha Srivastava, Shailendra K Gupta, Raja Feroz Ahmad

  Journal of molecular graphics & modelling. 01/2010; 28(7):664-9.

  Overexpression of HER-2 is of frequent (20-30%) occurrence in breast cancer. Therapeutic targeting of HER-2 with humanized antibody derived oligopeptide may be a promising approach to the treatment of breast cancer. HER-2 gene is part of a family of genes that play critical roles in regulating trans... [more] Overexpression of HER-2 is of frequent (20-30%) occurrence in breast cancer. Therapeutic targeting of HER-2 with humanized antibody derived oligopeptide may be a promising approach to the treatment of breast cancer. HER-2 gene is part of a family of genes that play critical roles in regulating transmembrane growth of breast cancer cells. Pertuzumab, a recombinant humanized monoclonal antibody (2C4), binds to extracellular domain II of the HER-2 receptor and inhibits its ability to dimerize with other HER receptors blocking the cell growth, signaling and apoptosis induction. The unique binding pocket on HER-2 for pertuzumab provides an important target domain for creation of new anticancer drugs. In the present work an efficient oligopeptide was designed by our computational method that interacts with pertuzumab binding sites of HER-2. In silico docking study demonstrated the best specific interaction of RASPADREV oligopeptide with the dimerization domain in the HER-2 molecule among various screened oligopeptides. ADMET and SAR properties prove the drug likeness of designed oligopeptide as having value 0.98.
• 3.62

  Impact points

  In silico DNA vaccine designing against human papillomavirus (HPV) causing cervical cancer.

  Shishir Kumar Gupta, Archana Singh, Mugdha Srivastava, Shailendra K Gupta, Bashir Akhlaq Akhoon

  Vaccine. 09/2009;

  HPV vaccines available in the market are not effective against different strains of papillomavirus, therefore, there is a need to develop a new prophylactic DNA vaccine which can work against different strains of HPVs and may lead to protection of cervical cancer against new pandemic viruses. We des... [more] HPV vaccines available in the market are not effective against different strains of papillomavirus, therefore, there is a need to develop a new prophylactic DNA vaccine which can work against different strains of HPVs and may lead to protection of cervical cancer against new pandemic viruses. We designed a potential prophylactic DNA vaccine by using all the consensus epitopic sequences of HPVs L2 capsid protein and performed in silico cloning of multiepitopic antigenic DNA sequence in pVAX-1 vector. Immunogenicity of vaccine has been enhanced by techniques like codon optimization, engineering CpG motifs, introducing promoters and co-injection with plasmids expressing immune-stimulatory molecules.

• Designing of drug for removal of methylation from Tcf21 gene in lung cancer

  Gupta SK, Singh A, Srivastava M

  Online Journal of Bioinformatics. 01/2009;

• In silico identification of novel protective VSG antigens expressed by Trypanosoma brucei and an effort for designing a highly immunogenic DNA vaccine using IL-12 as adjuvant

  Bashir Akhlaq Akhoon, Parvez Singh Slathia, Preeti Sharma, Shishir Kumar Gupta, Vijeshwar Verma

  Microbial Pathogenesis.

  African trypanosomiasis continues to be a major health problem, with more adults dying from this disease world-wide. As the sequence diversity of Trypanosoma brucei is extreme, with VSGs having 15–25% identity with most other VSGs, hence it displays a huge diversity of adaptations and host specifici... [more] African trypanosomiasis continues to be a major health problem, with more adults dying from this disease world-wide. As the sequence diversity of Trypanosoma brucei is extreme, with VSGs having 15–25% identity with most other VSGs, hence it displays a huge diversity of adaptations and host specificities. Therefore the need for an improved vaccine has become an international priority. The highly conserved and specific epitopes acting as both CD8+ and CD4+ T-cell epitopes (FLINKKPAL and FTALCTLAA) were predicted from large bunch of VSGs of T. brucei. Besides, some other potential epitopes with very high affinity for MHC I and II molecules were also determined while taking consideration on the most common HLA in the general population which accounts for major ethnicities. The vaccine candidates were found to be effective even for non-african populations as predicted by population coverage analysis. Hence the migrating travelers acting as a spread means of the infection can probably also be treated successfully after injection of such a multiepitopic vaccine. Exploiting the immunoinformatics approaches, we designed a potential vaccine by using the consensus epitopic sequence of 388 VSG proteins of T. brucei and performed in silico cloning of multiepitopic antigenic DNA sequence in pBI-CMV1 vector. Moreover, various techniques like codon adaptation, CpG optimization, removal of self recognized epitopes, use of adjuvant and co-injection with plasmids expressing immune-stimulatory molecules were implemented to enhance the immunogenicity of the proposed in silico vaccine.