International Journal of Scientific and Engineering Research, Jan 20, 2014
ABSTRACT Visceral Leishmaniasis (VL) is the most lethal form of Leishmaniasis caused by Leishmani... more ABSTRACT Visceral Leishmaniasis (VL) is the most lethal form of Leishmaniasis caused by Leishmania donovani. This disease is the second largest parasitic killer in the world. Trypanothione reductase (TR) is an enzyme commonly present in all members of Trypanosomatidae, including Leishmania. This enzyme, analogous to Glutathione Reductase (GR) of mammals, is crucial for the management of oxidative stress of the parasite; as it recycles Trypanothione. The three-dimensional structure of TR from L. donovani (LdTR) has not been determined till date. In this study, the three-dimensional structure of LdTR was built by homology modelling and refined using molecular dynamics program. Various properties of the structural hierarchy of LdTR was also attempted to study along with the recognition and characterization of catalytic domains present in the enzyme. The main tools and servers used for the research were- MODELLER 9.11, VEGA ZZ 3.01, and MESSA etc. The results involved creation of an energy-minimized, refined comparative 3-D model of LdTR. The study also predicted LdTR to be a mitochondrial protein that uses FAD as an electron donor and is involved directly involved in homo-dimerization as well as indirectly involved in reduction of reactive oxygen species. The structure was submitted in PMDB (Protein Model Database).
Journal of Pharmacy Research 6 (9) .pp. 913-918, Sep 13, 2013
Aim: Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme which plays a key role in fatty ac... more Aim: Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme which plays a key role in fatty acid biosynthesis via production of melonyl-CoA as an essential substrate. It is involved in homeostasis of fatty acids inside the system using both up and down regulating mechanisms. Apart from this In silico analysis of its catalytic site and regulatory sites make it a potential target for herbicidal and insecticidal drug targeting. Currently the 3D structure of Acetyl-CoA carboxylase (ACC) from Jatropha curcas has not been solved in Protein Data Bank (PDB). Hence the aim of the present study is to build the 3D structure of Acetyl-CoA carboxylase (ACC) from J. curcas also to perform a virtual screening for the identification of the effective inhibitors using molecular docking studies.
Methods: Homology modeling has been used to determine the 3D structure of Acetyl-CoA carboxylase (ACC) from J. curcas. Structure validation and molecular docking studies has been carried out using Procheck and Molegro Virtual Docker respectively.
Results: Ramachandran Plot confirmed quality of modeled structures along with main chain and side chain parameters. Out of 309 residues in SPDBV model, 244 were in core region 19 residues were in additional allowed region, 2 residues were in generous allowed region and no residues were in disallowed region.
Conclusion: Energy minimization for SPDBV model thermodynamically proved accepted structure with energy of −12,063.024 kJ/mol. The model further can be subjected to pharmacodynamic and pharmacokinetic studies. Molecular docking studies identified few established herbicides which could be promising inhibitors of Acetyl-CoA carboxylase (ACC). Efforts to screen and identify ACC inhibitors using flexible molecular docking resulted in Pinoxaden from Phenylpyrazole class as the most effective inhibitor with rerank = −81.436 and RMSD = 0.31.
Although attempts have been made to unveil protein-protein and host-pathogen interactions based o... more Although attempts have been made to unveil protein-protein and host-pathogen interactions based on molecular insights of important biological events and pathogenesis in various organisms, these efforts have not yet been reported in Corynebacterium pseudotuberculosis (Cp), the causative agent of Caseous Lymphadenitis (CLA). In this study, we used computational approaches to develop common conserved intra-species protein-protein interaction (PPI) networks first time for four Cp strains (Cp FRC41, Cp 316, ...
Although attempts have been made to unveil protein–protein and host–pathogen interactions based o... more Although attempts have been made to unveil protein–protein and host–pathogen interactions based on molecular insights of important biological events and pathogenesis in various organisms, these efforts have not yet been reported in Corynebacterium pseudotuberculosis (Cp), the causative agent of Caseous Lymphadenitis (CLA). In this study, we used computational approaches to develop common conserved intra-species protein–protein interaction (PPI) networks first time for four Cp strains (Cp FRC41, Cp 316, Cp 3/99-5, and Cp P54B96) followed by development of a common conserved inter-species bacterial PPI using conserved proteins in multiple pathogens (Y. pestis, M. tuberculosis, C. diphtheriae, C. ulcerans, E. coli, and all four Cp strains) and E. Coli based experimentally validated PPI data. Furthermore, the interacting proteins in the common conserved inter-species bacterial PPI were used to generate a conserved host–pathogen interaction (HP-PPI) network considering human, goat, sheep...
International Journal of Scientific and Engineering Research, Jan 20, 2014
ABSTRACT Visceral Leishmaniasis (VL) is the most lethal form of Leishmaniasis caused by Leishmani... more ABSTRACT Visceral Leishmaniasis (VL) is the most lethal form of Leishmaniasis caused by Leishmania donovani. This disease is the second largest parasitic killer in the world. Trypanothione reductase (TR) is an enzyme commonly present in all members of Trypanosomatidae, including Leishmania. This enzyme, analogous to Glutathione Reductase (GR) of mammals, is crucial for the management of oxidative stress of the parasite; as it recycles Trypanothione. The three-dimensional structure of TR from L. donovani (LdTR) has not been determined till date. In this study, the three-dimensional structure of LdTR was built by homology modelling and refined using molecular dynamics program. Various properties of the structural hierarchy of LdTR was also attempted to study along with the recognition and characterization of catalytic domains present in the enzyme. The main tools and servers used for the research were- MODELLER 9.11, VEGA ZZ 3.01, and MESSA etc. The results involved creation of an energy-minimized, refined comparative 3-D model of LdTR. The study also predicted LdTR to be a mitochondrial protein that uses FAD as an electron donor and is involved directly involved in homo-dimerization as well as indirectly involved in reduction of reactive oxygen species. The structure was submitted in PMDB (Protein Model Database).
Journal of Pharmacy Research 6 (9) .pp. 913-918, Sep 13, 2013
Aim: Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme which plays a key role in fatty ac... more Aim: Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme which plays a key role in fatty acid biosynthesis via production of melonyl-CoA as an essential substrate. It is involved in homeostasis of fatty acids inside the system using both up and down regulating mechanisms. Apart from this In silico analysis of its catalytic site and regulatory sites make it a potential target for herbicidal and insecticidal drug targeting. Currently the 3D structure of Acetyl-CoA carboxylase (ACC) from Jatropha curcas has not been solved in Protein Data Bank (PDB). Hence the aim of the present study is to build the 3D structure of Acetyl-CoA carboxylase (ACC) from J. curcas also to perform a virtual screening for the identification of the effective inhibitors using molecular docking studies.
Methods: Homology modeling has been used to determine the 3D structure of Acetyl-CoA carboxylase (ACC) from J. curcas. Structure validation and molecular docking studies has been carried out using Procheck and Molegro Virtual Docker respectively.
Results: Ramachandran Plot confirmed quality of modeled structures along with main chain and side chain parameters. Out of 309 residues in SPDBV model, 244 were in core region 19 residues were in additional allowed region, 2 residues were in generous allowed region and no residues were in disallowed region.
Conclusion: Energy minimization for SPDBV model thermodynamically proved accepted structure with energy of −12,063.024 kJ/mol. The model further can be subjected to pharmacodynamic and pharmacokinetic studies. Molecular docking studies identified few established herbicides which could be promising inhibitors of Acetyl-CoA carboxylase (ACC). Efforts to screen and identify ACC inhibitors using flexible molecular docking resulted in Pinoxaden from Phenylpyrazole class as the most effective inhibitor with rerank = −81.436 and RMSD = 0.31.
Although attempts have been made to unveil protein-protein and host-pathogen interactions based o... more Although attempts have been made to unveil protein-protein and host-pathogen interactions based on molecular insights of important biological events and pathogenesis in various organisms, these efforts have not yet been reported in Corynebacterium pseudotuberculosis (Cp), the causative agent of Caseous Lymphadenitis (CLA). In this study, we used computational approaches to develop common conserved intra-species protein-protein interaction (PPI) networks first time for four Cp strains (Cp FRC41, Cp 316, ...
Although attempts have been made to unveil protein–protein and host–pathogen interactions based o... more Although attempts have been made to unveil protein–protein and host–pathogen interactions based on molecular insights of important biological events and pathogenesis in various organisms, these efforts have not yet been reported in Corynebacterium pseudotuberculosis (Cp), the causative agent of Caseous Lymphadenitis (CLA). In this study, we used computational approaches to develop common conserved intra-species protein–protein interaction (PPI) networks first time for four Cp strains (Cp FRC41, Cp 316, Cp 3/99-5, and Cp P54B96) followed by development of a common conserved inter-species bacterial PPI using conserved proteins in multiple pathogens (Y. pestis, M. tuberculosis, C. diphtheriae, C. ulcerans, E. coli, and all four Cp strains) and E. Coli based experimentally validated PPI data. Furthermore, the interacting proteins in the common conserved inter-species bacterial PPI were used to generate a conserved host–pathogen interaction (HP-PPI) network considering human, goat, sheep...
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Papers by Ankit Verma
Methods: Homology modeling has been used to determine the 3D structure of Acetyl-CoA carboxylase (ACC) from J. curcas. Structure validation and molecular docking studies has been carried out using Procheck and Molegro Virtual Docker respectively.
Results: Ramachandran Plot confirmed quality of modeled structures along with main chain and side chain parameters. Out of 309 residues in SPDBV model, 244 were in core region 19 residues were in additional allowed region, 2 residues were in generous allowed region and no residues were in disallowed region.
Conclusion: Energy minimization for SPDBV model thermodynamically proved accepted structure with energy of −12,063.024 kJ/mol. The model further can be subjected to pharmacodynamic and pharmacokinetic studies. Molecular docking studies identified few established herbicides which could be promising inhibitors of Acetyl-CoA carboxylase (ACC). Efforts to screen and identify ACC inhibitors using flexible molecular docking resulted in Pinoxaden from Phenylpyrazole class as the most effective inhibitor with rerank = −81.436 and RMSD = 0.31.
Methods: Homology modeling has been used to determine the 3D structure of Acetyl-CoA carboxylase (ACC) from J. curcas. Structure validation and molecular docking studies has been carried out using Procheck and Molegro Virtual Docker respectively.
Results: Ramachandran Plot confirmed quality of modeled structures along with main chain and side chain parameters. Out of 309 residues in SPDBV model, 244 were in core region 19 residues were in additional allowed region, 2 residues were in generous allowed region and no residues were in disallowed region.
Conclusion: Energy minimization for SPDBV model thermodynamically proved accepted structure with energy of −12,063.024 kJ/mol. The model further can be subjected to pharmacodynamic and pharmacokinetic studies. Molecular docking studies identified few established herbicides which could be promising inhibitors of Acetyl-CoA carboxylase (ACC). Efforts to screen and identify ACC inhibitors using flexible molecular docking resulted in Pinoxaden from Phenylpyrazole class as the most effective inhibitor with rerank = −81.436 and RMSD = 0.31.