Dr. Dibyabhaba Pradhan | National Institute of Pathology, ICMR, New Delhi (original) (raw)

Papers by Dr. Dibyabhaba Pradhan

dbGAPs: A comprehensive database of genes and genetic markers associated with psoriasis and its subtypes

Genomics, Jan 12, 2017

Psoriasis is a systemic hyperproliferative inflammatory skin disorder, although rarely fatal but ... more Psoriasis is a systemic hyperproliferative inflammatory skin disorder, although rarely fatal but significantly reduces quality of life. Understanding the full genetic component of the disease association may provide insight into biological pathways as well as targets and biomarkers for diagnosis, prognosis and therapy. Studies related to psoriasis associated genes and genetic markers are scattered and not easily amendable to data-mining. To alleviate difficulties, we have developed dbGAPs an integrated knowledgebase representing a gateway to psoriasis associated genomic data. The database contains annotation for 202 manually curated genes associated with psoriasis and its subtypes with cross-references. Functional enrichment of these genes, in context of Gene Ontology and pathways, provide insight into their important role in psoriasis etiology and pathogenesis. The dbGAPs interface is enriched with an interactive search engine for data retrieval along with unique customized tools f...

A Leishmania-specific gene upregulated at the amastigote stage is crucial for parasite survival

Parasitology Research

TiD: Standalone software for mining putative drug targets from bacterial proteome

Genomics, 2016

Virtual human MEK1 protein inhibitors catechin and gw8510

International Journal of Scientific and Engineering Research, Mar 13, 2015

Neisseria meningitidis (N. meningitidis) is a non-motile, Gram-negative bacterium. N. meningitidi... more Neisseria meningitidis (N. meningitidis) is a non-motile, Gram-negative bacterium. N. meningitidis is often referred as meningococci and causes cerebrospinal fever and bacterial meningitis. Although antibiotics such as penicillin, ciprofloxacin, ceftriaxone, rifampin and polymixin were used to treat bacterial meningitis, but N. meningitidis exhibits multi drug resistance. Therefore, designing novel inhibitors against N. meningitidis would be useful for developing therapies directed towards management of cerebrospinal fever and bacterial meningitis. Genome sequence of N. meningitidis was explored using sRNAPredict tool to identify 249 sRNA candidates of which 68 were enzymes and rests were non enzymes. The enzyme GTP pyrophosphokinase plays a pivotal role in the growth and metabolisms of the pathogen and non-homologous to Homo sapiens, so it was selected as a potential drug target against N. meningitidis. Homology model was built to GTP pyrophosphokinase using Modeller 9v13. Model with lowest DOPE score was selected and validated using PROCHECK, ProSA and ProQ. Published inhibitors such as alpha beta ethylene-ATP, microccin, tetracycline, thiostrepton and viomycin were selected for shape based similarity screening against ASINEX database to generate an in-house library. Docking studies were accomplished using Glide v6.2 for in-house library with GTP pyrophosphokinase which revealed 39 potential leads. Binding free energies (ΔG score) of resulted leads and existing inhibitors were compared to propose five compounds as potent inhibitor of GTP pyrophosphokinase. Lead1 showed lowest ΔG score of -63.65 kcal/mol with strong hydrogen bonding network and with good van der Waals interactions. Five best leads are observed to obey the pharmacological properties at par with 95% of the existing drug molecule. Thus, the lead1 can freezes the functional activity of GTP pyrophosphokinase in the purine metabolism necessary for the replication and DNA repair, to halt proliferation of the of N. meningitidis.

161 Discovery of potent KdsA inhibitors of Leptospira interrogans through homology modeling, docking, and molecular dynamics simulations

Http Dx Doi Org 10 1080 07391102 2013 786403, May 29, 2013

176 Structure-based virtual screening towards identification of potential FabH inhibitors

Journal of Biomolecular Structure and Dynamics, May 29, 2013

Indian Journal of Virology, 2010

• The SVM-Prot functional annotation of VP2 protein had shown its Zinc binding, Coat and envelope... more • The SVM-Prot functional annotation of VP2 protein had shown its Zinc binding, Coat and envelope protein like and Calcium-binding properties. Higher Zinc binding property of the protein refers to its critical role in maintaining viral stability (Funk et al., 1992). Coat and envelope protein like properties signifies presence of the protein in viral outer membrane. Calcium ions appear to play a major role in maintaining the structural integrity and are likely involved in the process of viral uncoating (Rebecca et al., 1996).

Probing binding mechanism of interleukin-6 and olokizumab:in silicodesign of potential lead antibodies for autoimmune and inflammatory diseases

Journal of Receptors and Signal Transduction, 2016

Computer-aided antibody engineering has been successful in the design of new biologics for diseas... more Computer-aided antibody engineering has been successful in the design of new biologics for disease diagnosis and therapeutic interventions. Interleukin-6 (IL-6), a well-recognized drug target for various autoimmune and inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and psoriasis, was investigated in silico to design potential lead antibodies. Here, crystal structure of IL-6 along with monoclonal antibody olokizumab was explored to predict antigen-antibody (Ag - Ab)-interacting residues using DiscoTope, Paratome, and PyMOL. Tyr56, Tyr103 in heavy chain and Gly30, Ile31 in light chain of olokizumab were mutated with residues Ser, Thr, Tyr, Trp, and Phe. A set of 899 mutant macromolecules were designed, and binding affinity of these macromolecules to IL-6 was evaluated through Ag - Ab docking (ZDOCK, ClusPro, and Rosetta server), binding free-energy calculations using Molecular Mechanics/Poisson Boltzman Surface Area (MM/PBSA) method, and interaction energy estimation. In comparison to olokizumab, eight newly designed theoretical antibodies demonstrated better result in all assessments. Therefore, these newly designed macromolecules were proposed as potential lead antibodies to serve as a therapeutics option for IL-6-mediated diseases.

Para-(benzoyl)-phenylalanine as a potential inhibitor against LpxC of Leptospira spp.: homology modeling, docking, and molecular dynamics study

Http Dx Doi Org 10 1080 07391102 2012 758056, Feb 5, 2013

Leptospira interrogans, a Gram-negative bacterial pathogen is the main cause of human leptospiros... more Leptospira interrogans, a Gram-negative bacterial pathogen is the main cause of human leptospirosis. Lipid A is a highly immunoreactive endotoxic center of lipopolysaccharide (LPS) that anchors LPS into the outer membrane of Leptospira. Discovery of compounds inhibiting lipid-A biosynthetic pathway would be promising for dissolving the structural integrity of membrane leading to cell lysis and death of Leptospira. LpxC, a unique enzyme of lipid-A biosynthetic pathway was identified as common drug target of Leptospira. Herein, homology modeling, docking, and molecular dynamics (MD) simulations were employed to discover potential inhibitors of LpxC. A reliable tertiary structure of LpxC in complex with inhibitor BB-78485 was constructed in Modeller 9v8. A data-set of BB-78485 structural analogs were docked with LpxC in Maestro v9.2 virtual screening workflow, which implements three stage Glide docking protocol. Twelve lead molecules with better XP Gscore compared to BB-78485 were proposed as potential inhibitors of LpxC. Para-(benzoyl)-phenylalanine - that showed lowest XP Gscore (-10.35 kcal/mol) - was predicted to have best binding affinity towards LpxC. MD simulations were performed for LpxC and para-(benzoyl)-phenylalanine docking complex in Desmond v3.0. Trajectory analysis showed the docking complex and inter-molecular interactions was stable throughout the entire production part of MD simulations. The results indicate para-(benzoyl)-phenylalanine as a potent drug molecule against leptospirosis. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:10.

177 T-cell vaccine design for Streptococcus pneumoniae: an in silico approach

Http Dx Doi Org 10 1080 07391102 2013 786419, May 29, 2013

181 Discovery of potential inhibitors of BMX non-receptor tyrosine kinase through e-pharmacophore based virtual screening

Journal of biomolecular structure & dynamics, 2015

201 Structure guided novel lead molecules against ERK proteins: application of multiple docking and molecular dynamics studies

Journal of Biomolecular Structure and Dynamics, 2015

Computational approaches to identify common subunit vaccine candidates against bacterial meningitis

Interdisciplinary Sciences: Computational Life Sciences, 2013

Bacterial meningitis, an infection of the membranes (meninges) and cerebrospinal fluid (CSF) surr... more Bacterial meningitis, an infection of the membranes (meninges) and cerebrospinal fluid (CSF) surrounding the brain and spinal cord, is a major cause of death and disability all over the world. From perinatal period to adult, four common organisms responsible for most of the bacterial meningitis are Streptococcus pneumonia, Neisseria meningitidis, Haemophilus influenza and Staphylococcus aureus. As the disease is caused by more organisms, currently available vaccines for bacterial meningitis are specific and restricted to some of the serogroups or serotypes of each bacterium. In an effort to design common vaccine against bacterial meningitis, proteomes of the four pathogens were compared to extract seven common surface exposed ABC transporter proteins. Pro-Pred server was used to investigate the seven surface exposed proteins for promiscuous T-cell epitopes prediction. Predicted 22 T-cell epitopes were validated through published positive control, SYFPEITHI and immune epitope database to reduce the epitope dataset into seven. T-cell epitope 162-FMILPIFNV-170 of spermidine/putrescine ABC transporter permease (potH) protein was conserved across the four selected pathogens of bacterial meningitis. Hence, structural analysis was extended for epitope 162-FMILPIFNV-170. Crystal structures of HLA-DRB alleles were retrieved and structure of potH was modeled using Prime v3.0 for structural analysis. Computational docking of HLA-DRB alleles and epitope 162-FMILPIFNV-170 of potH was performed using Glide v5.7. RMSD and RMSF of simulation studies were analyzed by Desmond v3.2. The docking and simulation results revealed that the HLA-DRB-epitope complex was stable with interaction repressive function of HLA. Thus, the epitope would be ideal candidate for T-cell driven subunit vaccine design against bacterial meningitis.

Synthesis, biological evaluation, and molecular docking studies of N-(α-acetamido cinnamoyl) aryl hydrazone derivatives as antiinflammatory and analgesic agents

Medicinal Chemistry Research, 2014

Interdisciplinary Sciences: Computational Life Sciences, 2012

Epitopes of Leptospira inducing CD4 + T-cell responses by binding to human MHC molecules could cr... more Epitopes of Leptospira inducing CD4 + T-cell responses by binding to human MHC molecules could critically contribute to the development of subunit vaccines for leptospirosis. Herein, we have identified unique vaccine peptides from outer membrane proteins (OMPs) common to four sequenced pathogenic Leptospira serovars through in silico reverse vaccinology technique. The OMPs were explored for probable antigens using jemboss and screened in ProPred subsequently to predict thirty HLA-DRB epitopes. The HLA-DRB epitopes were validated through published positive control (HA307-PKYVKQNTLKLAT-319), SYFPEITHI and immune epitope database (IEDB) to list twelve epitopes as putative subunit vaccine peptides from nine OMPs. Cation efflux system membrane protein (czcA) having four subunit vaccine peptides, was modeled in Modeller9v7 and evaluated through Procheck, ProSA and ProQ. The HLA-DRB alleles and czcA 3D interactions were studied using Hex 5.1. Further, the T-cell epitopes present in czcA were docked individually with HLA-DRB alleles. The docking result revealed that czcA and its epitopes were interacting well with HLA-DRB alleles, hence would certainly produce cell mediated immune response in host. Thus, czcA and its four subunit vaccine peptides would be ideal T-cell driven efficacious vaccine against leptospirosis.

Nature Precedings, 2010

The incidence of infective endocarditis (IE) represents the fourth leading cause of life-threaten... more The incidence of infective endocarditis (IE) represents the fourth leading cause of life-threatening infectious disease with a yearly incidence of 15,000 to 20,000 new cases.

Nature Precedings, 2010

The whole proteome of human parvovirus b19 was retrieved from NCBI Refseq FTP server. The single-... more The whole proteome of human parvovirus b19 was retrieved from NCBI Refseq FTP server. The single-stranded genome contains 5596 nucleotides with the single nonstructural NS1 protein, two capsid proteins: VP1 and VP2. The RNAs expressed 7.5-Kda protein, 11-Kda protein and X protein. Structural protein VP1 shows that it is a coat protein belongs to calcium binding, zinc binding, magnesium binding and metal binding protein function families. Functions of 7.5kd protein and 11kd protein have not yet been determined experimentally. Analysis of 7.5kd protein by SVMProt shows that it belongs to outer membrane, lipid binding, coat protein, RNA binding structural protein (matrix protein, viral occlusion body, keratin) function families. It acts as an enzyme oxidoreductases-acting on a sulfur group of donars, isomerases -cis-trans isomerases.

Nature Precedings, 2010

The Ras-dependent Raf/MEK/ERK signaling pathway is a major regulator of cell proliferation and su... more The Ras-dependent Raf/MEK/ERK signaling pathway is a major regulator of cell proliferation and survival. MEK inhibitors may have broad utility in the treatment of human cancers driven by activation of this pathway due to the selective phosphorylation of ERK by MEK and the highly selective inhibition of MEK displayed by this class of inhibitors. In view of its importance, identification of potent inhibitor against MEK1 may be valuable to design effective drugs against melanoma. Inhibi-

Computerized Protein Modeling and Molecular Docking Analysis of Human Proto Oncogene Tyrosine Protein Kinase YES for Discovery of Novel Lead Molecules

Nature Precedings, 2010

ABSTRACT Human proto-oncogene tyrosine-protein kinase YES (YES) is a non receptor kinase belongs ... more ABSTRACT Human proto-oncogene tyrosine-protein kinase YES (YES) is a non receptor kinase belongs to Src family. This gene lies in close proximity to thymidylate synthase gene on chromosome 18, and a corresponding pseudogene has been found on chromosome 22. In hepatocellular carcinoma and colorectal carcinoma elevated human YES activity was observed. Inhibitors of human YES reported till date are in clinical trials and associated with several side effects. The present study was mainly aimed in homology modeling of human YES and discovery of novel lead molecules that inhibit YES kinase more efficiently with fewer side effects. Virtual screening and docking techniques were applied to identify novel lead molecule of YES kinase. As there was no reported human YES crystal structural data, the three dimensional structure of human YES was constructed based on template structure (PDB ID: 2H8H) obtained through homology search using MODELLER 9V7. The model was refined, energy minimized and assessed through PROCHECK. Active site residues of human YES were identified from the homology model in complex with template ligand AZD0530 and were further confirmed using CASTp. Five published inhibitors of YES family (Dasatinib, Bosutinib, SU6656, AZD0530 and CGP77675) were identified through literature search. High throughput virtual screening method at Ligand.Info was applied for these five inhibitors to establish a library of 1932 structural analogs. LigPrep was used to generate possible conformations of each ligand molecules from structural analog library. The ligand duplicates conformers, ligands having reactive functional group and poor ADME properties were rejected from the prepared dataset. Glide 5.5 was used to generate a grid box by picking the active site residues of human YES protein. Through sequential applications of stringent mode glide docking procedures from Glide HTVS to SP to XP respectively, 13 potential inhibitors were proposed. The docking complexes of each inhibitor with human YES protein were analyzed and lead ‘1’ molecule was identified to have higher binding affinity to human YES protein (XP Gscore: -12.07 Kcal/mol) compared to existing published inhibitors and other 12 lead molecules. The lead ‘1’ - human YES docking complex was highly stabilized through hydrogen bond network with amino acid residues Thr348, Asp358, Asp414 and Phe415. Moreover, from the results obtained we could decipher that lead ‘1’ molecule can be raised into potential inhibitors after binding assays, substantiated experimental investigations and passing several phases of clinical trials.

dbGAPs: A comprehensive database of genes and genetic markers associated with psoriasis and its subtypes

Genomics, Jan 12, 2017

Psoriasis is a systemic hyperproliferative inflammatory skin disorder, although rarely fatal but ... more Psoriasis is a systemic hyperproliferative inflammatory skin disorder, although rarely fatal but significantly reduces quality of life. Understanding the full genetic component of the disease association may provide insight into biological pathways as well as targets and biomarkers for diagnosis, prognosis and therapy. Studies related to psoriasis associated genes and genetic markers are scattered and not easily amendable to data-mining. To alleviate difficulties, we have developed dbGAPs an integrated knowledgebase representing a gateway to psoriasis associated genomic data. The database contains annotation for 202 manually curated genes associated with psoriasis and its subtypes with cross-references. Functional enrichment of these genes, in context of Gene Ontology and pathways, provide insight into their important role in psoriasis etiology and pathogenesis. The dbGAPs interface is enriched with an interactive search engine for data retrieval along with unique customized tools f...

A Leishmania-specific gene upregulated at the amastigote stage is crucial for parasite survival

Parasitology Research

TiD: Standalone software for mining putative drug targets from bacterial proteome

Genomics, 2016

Virtual human MEK1 protein inhibitors catechin and gw8510

International Journal of Scientific and Engineering Research, Mar 13, 2015

Neisseria meningitidis (N. meningitidis) is a non-motile, Gram-negative bacterium. N. meningitidi... more Neisseria meningitidis (N. meningitidis) is a non-motile, Gram-negative bacterium. N. meningitidis is often referred as meningococci and causes cerebrospinal fever and bacterial meningitis. Although antibiotics such as penicillin, ciprofloxacin, ceftriaxone, rifampin and polymixin were used to treat bacterial meningitis, but N. meningitidis exhibits multi drug resistance. Therefore, designing novel inhibitors against N. meningitidis would be useful for developing therapies directed towards management of cerebrospinal fever and bacterial meningitis. Genome sequence of N. meningitidis was explored using sRNAPredict tool to identify 249 sRNA candidates of which 68 were enzymes and rests were non enzymes. The enzyme GTP pyrophosphokinase plays a pivotal role in the growth and metabolisms of the pathogen and non-homologous to Homo sapiens, so it was selected as a potential drug target against N. meningitidis. Homology model was built to GTP pyrophosphokinase using Modeller 9v13. Model with lowest DOPE score was selected and validated using PROCHECK, ProSA and ProQ. Published inhibitors such as alpha beta ethylene-ATP, microccin, tetracycline, thiostrepton and viomycin were selected for shape based similarity screening against ASINEX database to generate an in-house library. Docking studies were accomplished using Glide v6.2 for in-house library with GTP pyrophosphokinase which revealed 39 potential leads. Binding free energies (ΔG score) of resulted leads and existing inhibitors were compared to propose five compounds as potent inhibitor of GTP pyrophosphokinase. Lead1 showed lowest ΔG score of -63.65 kcal/mol with strong hydrogen bonding network and with good van der Waals interactions. Five best leads are observed to obey the pharmacological properties at par with 95% of the existing drug molecule. Thus, the lead1 can freezes the functional activity of GTP pyrophosphokinase in the purine metabolism necessary for the replication and DNA repair, to halt proliferation of the of N. meningitidis.

161 Discovery of potent KdsA inhibitors of Leptospira interrogans through homology modeling, docking, and molecular dynamics simulations

Http Dx Doi Org 10 1080 07391102 2013 786403, May 29, 2013

176 Structure-based virtual screening towards identification of potential FabH inhibitors

Journal of Biomolecular Structure and Dynamics, May 29, 2013

Indian Journal of Virology, 2010

• The SVM-Prot functional annotation of VP2 protein had shown its Zinc binding, Coat and envelope... more • The SVM-Prot functional annotation of VP2 protein had shown its Zinc binding, Coat and envelope protein like and Calcium-binding properties. Higher Zinc binding property of the protein refers to its critical role in maintaining viral stability (Funk et al., 1992). Coat and envelope protein like properties signifies presence of the protein in viral outer membrane. Calcium ions appear to play a major role in maintaining the structural integrity and are likely involved in the process of viral uncoating (Rebecca et al., 1996).

Probing binding mechanism of interleukin-6 and olokizumab:in silicodesign of potential lead antibodies for autoimmune and inflammatory diseases

Journal of Receptors and Signal Transduction, 2016

Computer-aided antibody engineering has been successful in the design of new biologics for diseas... more Computer-aided antibody engineering has been successful in the design of new biologics for disease diagnosis and therapeutic interventions. Interleukin-6 (IL-6), a well-recognized drug target for various autoimmune and inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and psoriasis, was investigated in silico to design potential lead antibodies. Here, crystal structure of IL-6 along with monoclonal antibody olokizumab was explored to predict antigen-antibody (Ag - Ab)-interacting residues using DiscoTope, Paratome, and PyMOL. Tyr56, Tyr103 in heavy chain and Gly30, Ile31 in light chain of olokizumab were mutated with residues Ser, Thr, Tyr, Trp, and Phe. A set of 899 mutant macromolecules were designed, and binding affinity of these macromolecules to IL-6 was evaluated through Ag - Ab docking (ZDOCK, ClusPro, and Rosetta server), binding free-energy calculations using Molecular Mechanics/Poisson Boltzman Surface Area (MM/PBSA) method, and interaction energy estimation. In comparison to olokizumab, eight newly designed theoretical antibodies demonstrated better result in all assessments. Therefore, these newly designed macromolecules were proposed as potential lead antibodies to serve as a therapeutics option for IL-6-mediated diseases.

Para-(benzoyl)-phenylalanine as a potential inhibitor against LpxC of Leptospira spp.: homology modeling, docking, and molecular dynamics study

Http Dx Doi Org 10 1080 07391102 2012 758056, Feb 5, 2013

Leptospira interrogans, a Gram-negative bacterial pathogen is the main cause of human leptospiros... more Leptospira interrogans, a Gram-negative bacterial pathogen is the main cause of human leptospirosis. Lipid A is a highly immunoreactive endotoxic center of lipopolysaccharide (LPS) that anchors LPS into the outer membrane of Leptospira. Discovery of compounds inhibiting lipid-A biosynthetic pathway would be promising for dissolving the structural integrity of membrane leading to cell lysis and death of Leptospira. LpxC, a unique enzyme of lipid-A biosynthetic pathway was identified as common drug target of Leptospira. Herein, homology modeling, docking, and molecular dynamics (MD) simulations were employed to discover potential inhibitors of LpxC. A reliable tertiary structure of LpxC in complex with inhibitor BB-78485 was constructed in Modeller 9v8. A data-set of BB-78485 structural analogs were docked with LpxC in Maestro v9.2 virtual screening workflow, which implements three stage Glide docking protocol. Twelve lead molecules with better XP Gscore compared to BB-78485 were proposed as potential inhibitors of LpxC. Para-(benzoyl)-phenylalanine - that showed lowest XP Gscore (-10.35 kcal/mol) - was predicted to have best binding affinity towards LpxC. MD simulations were performed for LpxC and para-(benzoyl)-phenylalanine docking complex in Desmond v3.0. Trajectory analysis showed the docking complex and inter-molecular interactions was stable throughout the entire production part of MD simulations. The results indicate para-(benzoyl)-phenylalanine as a potent drug molecule against leptospirosis. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:10.

177 T-cell vaccine design for Streptococcus pneumoniae: an in silico approach

Http Dx Doi Org 10 1080 07391102 2013 786419, May 29, 2013

181 Discovery of potential inhibitors of BMX non-receptor tyrosine kinase through e-pharmacophore based virtual screening

Journal of biomolecular structure & dynamics, 2015

201 Structure guided novel lead molecules against ERK proteins: application of multiple docking and molecular dynamics studies

Journal of Biomolecular Structure and Dynamics, 2015

Computational approaches to identify common subunit vaccine candidates against bacterial meningitis

Interdisciplinary Sciences: Computational Life Sciences, 2013

Bacterial meningitis, an infection of the membranes (meninges) and cerebrospinal fluid (CSF) surr... more Bacterial meningitis, an infection of the membranes (meninges) and cerebrospinal fluid (CSF) surrounding the brain and spinal cord, is a major cause of death and disability all over the world. From perinatal period to adult, four common organisms responsible for most of the bacterial meningitis are Streptococcus pneumonia, Neisseria meningitidis, Haemophilus influenza and Staphylococcus aureus. As the disease is caused by more organisms, currently available vaccines for bacterial meningitis are specific and restricted to some of the serogroups or serotypes of each bacterium. In an effort to design common vaccine against bacterial meningitis, proteomes of the four pathogens were compared to extract seven common surface exposed ABC transporter proteins. Pro-Pred server was used to investigate the seven surface exposed proteins for promiscuous T-cell epitopes prediction. Predicted 22 T-cell epitopes were validated through published positive control, SYFPEITHI and immune epitope database to reduce the epitope dataset into seven. T-cell epitope 162-FMILPIFNV-170 of spermidine/putrescine ABC transporter permease (potH) protein was conserved across the four selected pathogens of bacterial meningitis. Hence, structural analysis was extended for epitope 162-FMILPIFNV-170. Crystal structures of HLA-DRB alleles were retrieved and structure of potH was modeled using Prime v3.0 for structural analysis. Computational docking of HLA-DRB alleles and epitope 162-FMILPIFNV-170 of potH was performed using Glide v5.7. RMSD and RMSF of simulation studies were analyzed by Desmond v3.2. The docking and simulation results revealed that the HLA-DRB-epitope complex was stable with interaction repressive function of HLA. Thus, the epitope would be ideal candidate for T-cell driven subunit vaccine design against bacterial meningitis.

Synthesis, biological evaluation, and molecular docking studies of N-(α-acetamido cinnamoyl) aryl hydrazone derivatives as antiinflammatory and analgesic agents

Medicinal Chemistry Research, 2014

Interdisciplinary Sciences: Computational Life Sciences, 2012

Epitopes of Leptospira inducing CD4 + T-cell responses by binding to human MHC molecules could cr... more Epitopes of Leptospira inducing CD4 + T-cell responses by binding to human MHC molecules could critically contribute to the development of subunit vaccines for leptospirosis. Herein, we have identified unique vaccine peptides from outer membrane proteins (OMPs) common to four sequenced pathogenic Leptospira serovars through in silico reverse vaccinology technique. The OMPs were explored for probable antigens using jemboss and screened in ProPred subsequently to predict thirty HLA-DRB epitopes. The HLA-DRB epitopes were validated through published positive control (HA307-PKYVKQNTLKLAT-319), SYFPEITHI and immune epitope database (IEDB) to list twelve epitopes as putative subunit vaccine peptides from nine OMPs. Cation efflux system membrane protein (czcA) having four subunit vaccine peptides, was modeled in Modeller9v7 and evaluated through Procheck, ProSA and ProQ. The HLA-DRB alleles and czcA 3D interactions were studied using Hex 5.1. Further, the T-cell epitopes present in czcA were docked individually with HLA-DRB alleles. The docking result revealed that czcA and its epitopes were interacting well with HLA-DRB alleles, hence would certainly produce cell mediated immune response in host. Thus, czcA and its four subunit vaccine peptides would be ideal T-cell driven efficacious vaccine against leptospirosis.

Nature Precedings, 2010

The incidence of infective endocarditis (IE) represents the fourth leading cause of life-threaten... more The incidence of infective endocarditis (IE) represents the fourth leading cause of life-threatening infectious disease with a yearly incidence of 15,000 to 20,000 new cases.

Nature Precedings, 2010

The whole proteome of human parvovirus b19 was retrieved from NCBI Refseq FTP server. The single-... more The whole proteome of human parvovirus b19 was retrieved from NCBI Refseq FTP server. The single-stranded genome contains 5596 nucleotides with the single nonstructural NS1 protein, two capsid proteins: VP1 and VP2. The RNAs expressed 7.5-Kda protein, 11-Kda protein and X protein. Structural protein VP1 shows that it is a coat protein belongs to calcium binding, zinc binding, magnesium binding and metal binding protein function families. Functions of 7.5kd protein and 11kd protein have not yet been determined experimentally. Analysis of 7.5kd protein by SVMProt shows that it belongs to outer membrane, lipid binding, coat protein, RNA binding structural protein (matrix protein, viral occlusion body, keratin) function families. It acts as an enzyme oxidoreductases-acting on a sulfur group of donars, isomerases -cis-trans isomerases.

Nature Precedings, 2010

The Ras-dependent Raf/MEK/ERK signaling pathway is a major regulator of cell proliferation and su... more The Ras-dependent Raf/MEK/ERK signaling pathway is a major regulator of cell proliferation and survival. MEK inhibitors may have broad utility in the treatment of human cancers driven by activation of this pathway due to the selective phosphorylation of ERK by MEK and the highly selective inhibition of MEK displayed by this class of inhibitors. In view of its importance, identification of potent inhibitor against MEK1 may be valuable to design effective drugs against melanoma. Inhibi-

Computerized Protein Modeling and Molecular Docking Analysis of Human Proto Oncogene Tyrosine Protein Kinase YES for Discovery of Novel Lead Molecules

Nature Precedings, 2010

ABSTRACT Human proto-oncogene tyrosine-protein kinase YES (YES) is a non receptor kinase belongs ... more ABSTRACT Human proto-oncogene tyrosine-protein kinase YES (YES) is a non receptor kinase belongs to Src family. This gene lies in close proximity to thymidylate synthase gene on chromosome 18, and a corresponding pseudogene has been found on chromosome 22. In hepatocellular carcinoma and colorectal carcinoma elevated human YES activity was observed. Inhibitors of human YES reported till date are in clinical trials and associated with several side effects. The present study was mainly aimed in homology modeling of human YES and discovery of novel lead molecules that inhibit YES kinase more efficiently with fewer side effects. Virtual screening and docking techniques were applied to identify novel lead molecule of YES kinase. As there was no reported human YES crystal structural data, the three dimensional structure of human YES was constructed based on template structure (PDB ID: 2H8H) obtained through homology search using MODELLER 9V7. The model was refined, energy minimized and assessed through PROCHECK. Active site residues of human YES were identified from the homology model in complex with template ligand AZD0530 and were further confirmed using CASTp. Five published inhibitors of YES family (Dasatinib, Bosutinib, SU6656, AZD0530 and CGP77675) were identified through literature search. High throughput virtual screening method at Ligand.Info was applied for these five inhibitors to establish a library of 1932 structural analogs. LigPrep was used to generate possible conformations of each ligand molecules from structural analog library. The ligand duplicates conformers, ligands having reactive functional group and poor ADME properties were rejected from the prepared dataset. Glide 5.5 was used to generate a grid box by picking the active site residues of human YES protein. Through sequential applications of stringent mode glide docking procedures from Glide HTVS to SP to XP respectively, 13 potential inhibitors were proposed. The docking complexes of each inhibitor with human YES protein were analyzed and lead ‘1’ molecule was identified to have higher binding affinity to human YES protein (XP Gscore: -12.07 Kcal/mol) compared to existing published inhibitors and other 12 lead molecules. The lead ‘1’ - human YES docking complex was highly stabilized through hydrogen bond network with amino acid residues Thr348, Asp358, Asp414 and Phe415. Moreover, from the results obtained we could decipher that lead ‘1’ molecule can be raised into potential inhibitors after binding assays, substantiated experimental investigations and passing several phases of clinical trials.