RAVI KUMAR RAWAT - Academia.edu (original) (raw)
Uploads
Papers by RAVI KUMAR RAWAT
![Research paper thumbnail of [Copyright] [SW-14260/2021] HERO Automagical MD Analysis and Plotting Script](https://attachments.academia-assets.com/102964448/thumbnails/1.jpg)
](Computer software work: Hero automagical MD Analysis and plotting script is a program for the Ana... more Computer software work: Hero automagical MD Analysis and plotting script is a program for the Analysis and plotting of particle-based Trajectories in .xtc format generated from Molecular dynamics MD simulations using GROMACS.
Future Medicinal Chemistry, 2021
Background & objective: Molecular dynamics simulations (MDS) using GROMACS are among the commonly... more Background & objective: Molecular dynamics simulations (MDS) using GROMACS are among the commonly used computational experiments in the area of molecular biology and drug discovery. This article presents a project called HeroMDAnalysis, an automagical tool to analyze the GROMACS-based MDS trajectories and generate plots as high-quality images for various parameters. Materials & methods: The tool was built using bash shell programming, and graphical user interface was built using Zenity engine. Results & conclusion: This tool offers a simple, semiautomated, and relatively fast framework for what was previously a complex, manual, time-consuming and error-prone task, presenting a useful method for biochemists and synthetic chemists with no prior experience of the command line interface.
Journal of Biomolecular Structure and Dynamics, 2020
Emerging cases of drug resistance against Artemisinin combination therapies which are the current... more Emerging cases of drug resistance against Artemisinin combination therapies which are the current and the last line of defense against malaria makes the situation very alarming. Due to the liability of single-target drugs to be more prone to drug resistance, the trend of development of dual or multitarget inhibitors is emerging. Recently, a malaria box molecule, MMV007571 which is a well known new permeability pathways inhibitor was investigated to be also multi-targeting Plasmodium falciparum dihydroorotate dehydrogenase and cytochrome bc1 complex. The aspiration behind this study was to use the information of its pharmacophoric features essential for binding as two of its new targets. In this regard, high throughput virtual screening involving pharmacophore mapping, ADME filtering, molecular docking, and MM-GBSA calculations were carried out. This approach has lead to the identification of two new hits namely DT00V1902 and DT00V1922 which binds with-37.85 and-24.65 kcal/mol of more stable DG Bind energy at two targets than the lead molecule, MMV007571. The screened compounds are indicated to be carry improvement in binding potential and pharmacokinetic characters as per in silico studies. The authors propose that DT00V1902 and DT00V1922 can be forwarded for experimental validation and clinical studies for antimalarial chemotherapy.
![Research paper thumbnail of Advancements in chemical methodologies for the synthesis of 3-aroylimidazo[1,2-a]pyridines: an update of the decade](https://attachments.academia-assets.com/102964415/thumbnails/1.jpg)
](Synthetic Communications, 2020
Prisma Buchtipps haftpflichtrecht. Im dritten Teil "Zustandsbegutachtung II" werden Pflegeversich... more Prisma Buchtipps haftpflichtrecht. Im dritten Teil "Zustandsbegutachtung II" werden Pflegeversicherung, private Kranken-, Krankentagegeldund Berufsunfähigkeitsversicherung behandelt. Am Ende eines jeden Kapitels sind Gutachtenbeispiele aufgeführt und kommentiert. Der letzte Teil des Buches widmet sich "speziellen Begutachtungsfragen" (u.a. Besonderheiten der psychiatrischen und forensischen Begutachtung, Begutachtung von Migranten, Begutachtung von Schmerzsyndromen sowie medizinische Begutachtung aus richterlicher Sicht). Als Einstiegsliteratur kann das vorliegende Buch vorbehaltlos jedem empfohlen werden, der sich allgemein mit gut
![Research paper thumbnail of Pd2(dba)3-catalyzed amination of C5-bromo-imidazo[2,1-b][1,3,4] thiadiazole with substituted anilines at conventional heating in Schlenk tube](https://attachments.academia-assets.com/102964445/thumbnails/1.jpg)
](Journal of Sulfur Chemistry, 2020
An efficient Pd 2 (dba) 3-catalyzed amination of C5-bromo-imidazo[2, 1-b][1,3,4]thiadiazole using... more An efficient Pd 2 (dba) 3-catalyzed amination of C5-bromo-imidazo[2, 1-b][1,3,4]thiadiazole using conventional heating is reported. The C5-bromoimidazo[2,1-b][1,3,4]thiadiazole was synthesized using a multistep approach which started by cyclization of thiosemicarbazide with a carboxylic acid to give 2-amino[1,3,4]thiadiazoles which were further treated with 2-haloketones to give imidazo[2,1b][1,3,4]thiadiazoles. Then, the bromination of imidazothiadiazole was done using N-bromosuccinimide to give the C5-bromo-imidazo [2,1-b][1,3,4]thiadiazole. Afterward, various C-N bond-forming approaches were attempted such as S N Ar, Cu(I), Cu(II), Pd(OAc) 2, Pd 2 (dba) 3 catalyst with different ligand, additive, base, solvent and temperature conditions. Out of various approaches used, only Buchwald Hartwig amination, performed with conventional heating, gave N-arylamine-5-imidazothiadiazoles. Then, 10 different anilines with different electron-withdrawing and donating groups at different positions were employed to examine the scope and limitations of the method. Salient features of this method include conventional heating in a Schlenk tube as the reaction condition, the absence of the use of toxic isocyanides, the wide nature of substituent tolerance with anilines, and moderately good product yields.
Journal of Biomolecular Structure and Dynamics, 2020
A recent research has identified chymase, a mast cell-specific protease as an exclusive novel the... more A recent research has identified chymase, a mast cell-specific protease as an exclusive novel therapeutic target to prevent Japanese encephalitis virus (JEV) induced encephalitis. Interestingly, JEV activates mast cell specific chymase during its penetration through blood brain barrier (BBB) which eventually guide to viral encephalitis. Hence, in this study, natural chemical entities (NCE) from multiple databases (MPD3, TIPDB and MTDP) were virtually screened for their binding affinity as chymase inhibitors, a promising negotiator for prolong survival against JEV tempted encephalitis. Merged computational programs, Maestro software, QikProp, ProTox and Gromacs were applied to screen the NCEs against target receptor (PDB: 4KP0). Three hits (C00008437, C00014417 and 8141903) were identified after employing a series of sieves such as High Throughput Virtual Screening (HTVS), Standard precision (SP) and Xtra precision (XP) molecular docking simulations followed by desired pharmacokinetic-toxicity profile predictions and molecular dynamics (MD) examinations. Maestro simulations resulted in best three binding energy scores as-11.992 kcal/mol (first ranked; C00008437),-11.673 kcal/mol (second ranked; C00014417) and-11.456 kcal/mol (third ranked; 8141903), respectively. The top three hits revealed an ideal range of pharmacokinetic and toxicity descriptors values. In addition, MD simulations enabled us to confirm top hits higher selectivity toward chymase receptor. In conclusion, this might potentially represent remarkable novel classes with an effective chymase mediated treatment to combat JEV induced encephalitis, which need to justify with further detail studies.
Journal of Biomolecular Structure and Dynamics, 2019
Recently, two Malaria Box molecules namely MMV007571 and MMV020439 well known inhibitors of New P... more Recently, two Malaria Box molecules namely MMV007571 and MMV020439 well known inhibitors of New Permeability Pathway (NPP) function also showed a secondary phenotype of inhibition of enzyme Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) and cytochrome bc1 complex in metabolic profile assays. Intricacies of their binding at the newly identified targets was need of the hour which motivated us to study their binding using molecular docking and dynamics simulations approach. Interestingly, molecular docking results of both MMV007571 and MMV020439 showed good binding affinity toward the Q o site of cytochrome bc1 complex while only MMV007571 illustrated notable binding characterstics for PfDHODH. Molecular Dynamics (MD) simulations when carried out for native-PfDHODH, PfDHODH-MMV007571 and PfDHODH-Genz667348 models (100 ns each) demonstrated the role of inhibitors over the N-terminus domain which experienced conformational transition from an open state (22 Å) to closed state (16 Å) in the proteininhibitor models. Dynamics also indicated that the loop domain near cofactor flavin mononucleotide (FMN) attained more felxibility which further lead to its poor binding and may contribute to inhibition of the oxidation (catalytic) process. Moreover, the pharmacophoric features of MMV007571 was justified and may serve as a template for the design of novel series of more potent multitarget inhibitors against Plasmodium falciparum.
Journal of Biomolecular Structure and Dynamics, 2019
Macrophage mannose receptor (MMR) is a C-type lectin that regulates the phagocytosis and phagocyt... more Macrophage mannose receptor (MMR) is a C-type lectin that regulates the phagocytosis and phagocytosis-lysosome (P-L) fusion in tuberculosis. Mannose-capped lipoarabinomannan (ManLAM), a lipoglycan present at the surface of Mycobacterium tuberculosis (MT), is an important factor in phagocyte attachment and internalization that is specific for MMR. Based on this idea, herein we have designed our experiment to understand the better site-specific delivery against tuberculosis. An experimental outcome was used as a basis to revisit the reverse experimental strategy for tuberculosis management. Stearic mannose was prepared from stearic acid incubation with the D-mannose. Interestingly, stearic mannose explained its internalisation via stimulating actin-mediated phagocytic pathway of MMR experimentally. Following, an in silico strategy towards hypothetical designing of A c c e p t e d M a n u s c r i p t various mannose-stearyl conjugates (SBKK1-7) against tuberculosis, as binding promoter of MMR (PDB: 1EGI), was carried out using molecular docking and dynamics approaches. Overall, SPKK-5 viz. ortho stearic mannose (OSM) showed a higher binding affinity with notable H-bonding and hydrophobic interactions. Pharmacokinetic and toxicity examinations illustrated an ideal range of descriptors values for apex screened compounds. Molecular dynamics simulations have confirmed its significant intactness with the MMR. Ultimately, the whole effort led to the identification of promising hit (SBKK-5), which positively correlates with the experimental work and furthermore need to explore its novel drug delivery systems with improved anti-tubercular therapy.
Computer software work: Hero automagical MD Analysis and plotting script is a program for the Ana... more Computer software work: Hero automagical MD Analysis and plotting script is a program for the Analysis and plotting of particle-based Trajectories in .xtc format generated from Molecular dynamics MD simulations using GROMACS.
Future Medicinal Chemistry, 2021
Background & objective: Molecular dynamics simulations (MDS) using GROMACS are among the commonly... more Background & objective: Molecular dynamics simulations (MDS) using GROMACS are among the commonly used computational experiments in the area of molecular biology and drug discovery. This article presents a project called HeroMDAnalysis, an automagical tool to analyze the GROMACS-based MDS trajectories and generate plots as high-quality images for various parameters. Materials & methods: The tool was built using bash shell programming, and graphical user interface was built using Zenity engine. Results & conclusion: This tool offers a simple, semiautomated, and relatively fast framework for what was previously a complex, manual, time-consuming and error-prone task, presenting a useful method for biochemists and synthetic chemists with no prior experience of the command line interface.
Journal of Biomolecular Structure and Dynamics, 2020
Emerging cases of drug resistance against Artemisinin combination therapies which are the current... more Emerging cases of drug resistance against Artemisinin combination therapies which are the current and the last line of defense against malaria makes the situation very alarming. Due to the liability of single-target drugs to be more prone to drug resistance, the trend of development of dual or multitarget inhibitors is emerging. Recently, a malaria box molecule, MMV007571 which is a well known new permeability pathways inhibitor was investigated to be also multi-targeting Plasmodium falciparum dihydroorotate dehydrogenase and cytochrome bc1 complex. The aspiration behind this study was to use the information of its pharmacophoric features essential for binding as two of its new targets. In this regard, high throughput virtual screening involving pharmacophore mapping, ADME filtering, molecular docking, and MM-GBSA calculations were carried out. This approach has lead to the identification of two new hits namely DT00V1902 and DT00V1922 which binds with-37.85 and-24.65 kcal/mol of more stable DG Bind energy at two targets than the lead molecule, MMV007571. The screened compounds are indicated to be carry improvement in binding potential and pharmacokinetic characters as per in silico studies. The authors propose that DT00V1902 and DT00V1922 can be forwarded for experimental validation and clinical studies for antimalarial chemotherapy.
Synthetic Communications, 2020
Prisma Buchtipps haftpflichtrecht. Im dritten Teil "Zustandsbegutachtung II" werden Pflegeversich... more Prisma Buchtipps haftpflichtrecht. Im dritten Teil "Zustandsbegutachtung II" werden Pflegeversicherung, private Kranken-, Krankentagegeldund Berufsunfähigkeitsversicherung behandelt. Am Ende eines jeden Kapitels sind Gutachtenbeispiele aufgeführt und kommentiert. Der letzte Teil des Buches widmet sich "speziellen Begutachtungsfragen" (u.a. Besonderheiten der psychiatrischen und forensischen Begutachtung, Begutachtung von Migranten, Begutachtung von Schmerzsyndromen sowie medizinische Begutachtung aus richterlicher Sicht). Als Einstiegsliteratur kann das vorliegende Buch vorbehaltlos jedem empfohlen werden, der sich allgemein mit gut
Journal of Sulfur Chemistry, 2020
An efficient Pd 2 (dba) 3-catalyzed amination of C5-bromo-imidazo[2, 1-b][1,3,4]thiadiazole using... more An efficient Pd 2 (dba) 3-catalyzed amination of C5-bromo-imidazo[2, 1-b][1,3,4]thiadiazole using conventional heating is reported. The C5-bromoimidazo[2,1-b][1,3,4]thiadiazole was synthesized using a multistep approach which started by cyclization of thiosemicarbazide with a carboxylic acid to give 2-amino[1,3,4]thiadiazoles which were further treated with 2-haloketones to give imidazo[2,1b][1,3,4]thiadiazoles. Then, the bromination of imidazothiadiazole was done using N-bromosuccinimide to give the C5-bromo-imidazo [2,1-b][1,3,4]thiadiazole. Afterward, various C-N bond-forming approaches were attempted such as S N Ar, Cu(I), Cu(II), Pd(OAc) 2, Pd 2 (dba) 3 catalyst with different ligand, additive, base, solvent and temperature conditions. Out of various approaches used, only Buchwald Hartwig amination, performed with conventional heating, gave N-arylamine-5-imidazothiadiazoles. Then, 10 different anilines with different electron-withdrawing and donating groups at different positions were employed to examine the scope and limitations of the method. Salient features of this method include conventional heating in a Schlenk tube as the reaction condition, the absence of the use of toxic isocyanides, the wide nature of substituent tolerance with anilines, and moderately good product yields.
Journal of Biomolecular Structure and Dynamics, 2020
A recent research has identified chymase, a mast cell-specific protease as an exclusive novel the... more A recent research has identified chymase, a mast cell-specific protease as an exclusive novel therapeutic target to prevent Japanese encephalitis virus (JEV) induced encephalitis. Interestingly, JEV activates mast cell specific chymase during its penetration through blood brain barrier (BBB) which eventually guide to viral encephalitis. Hence, in this study, natural chemical entities (NCE) from multiple databases (MPD3, TIPDB and MTDP) were virtually screened for their binding affinity as chymase inhibitors, a promising negotiator for prolong survival against JEV tempted encephalitis. Merged computational programs, Maestro software, QikProp, ProTox and Gromacs were applied to screen the NCEs against target receptor (PDB: 4KP0). Three hits (C00008437, C00014417 and 8141903) were identified after employing a series of sieves such as High Throughput Virtual Screening (HTVS), Standard precision (SP) and Xtra precision (XP) molecular docking simulations followed by desired pharmacokinetic-toxicity profile predictions and molecular dynamics (MD) examinations. Maestro simulations resulted in best three binding energy scores as-11.992 kcal/mol (first ranked; C00008437),-11.673 kcal/mol (second ranked; C00014417) and-11.456 kcal/mol (third ranked; 8141903), respectively. The top three hits revealed an ideal range of pharmacokinetic and toxicity descriptors values. In addition, MD simulations enabled us to confirm top hits higher selectivity toward chymase receptor. In conclusion, this might potentially represent remarkable novel classes with an effective chymase mediated treatment to combat JEV induced encephalitis, which need to justify with further detail studies.
Journal of Biomolecular Structure and Dynamics, 2019
Recently, two Malaria Box molecules namely MMV007571 and MMV020439 well known inhibitors of New P... more Recently, two Malaria Box molecules namely MMV007571 and MMV020439 well known inhibitors of New Permeability Pathway (NPP) function also showed a secondary phenotype of inhibition of enzyme Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) and cytochrome bc1 complex in metabolic profile assays. Intricacies of their binding at the newly identified targets was need of the hour which motivated us to study their binding using molecular docking and dynamics simulations approach. Interestingly, molecular docking results of both MMV007571 and MMV020439 showed good binding affinity toward the Q o site of cytochrome bc1 complex while only MMV007571 illustrated notable binding characterstics for PfDHODH. Molecular Dynamics (MD) simulations when carried out for native-PfDHODH, PfDHODH-MMV007571 and PfDHODH-Genz667348 models (100 ns each) demonstrated the role of inhibitors over the N-terminus domain which experienced conformational transition from an open state (22 Å) to closed state (16 Å) in the proteininhibitor models. Dynamics also indicated that the loop domain near cofactor flavin mononucleotide (FMN) attained more felxibility which further lead to its poor binding and may contribute to inhibition of the oxidation (catalytic) process. Moreover, the pharmacophoric features of MMV007571 was justified and may serve as a template for the design of novel series of more potent multitarget inhibitors against Plasmodium falciparum.
Journal of Biomolecular Structure and Dynamics, 2019
Macrophage mannose receptor (MMR) is a C-type lectin that regulates the phagocytosis and phagocyt... more Macrophage mannose receptor (MMR) is a C-type lectin that regulates the phagocytosis and phagocytosis-lysosome (P-L) fusion in tuberculosis. Mannose-capped lipoarabinomannan (ManLAM), a lipoglycan present at the surface of Mycobacterium tuberculosis (MT), is an important factor in phagocyte attachment and internalization that is specific for MMR. Based on this idea, herein we have designed our experiment to understand the better site-specific delivery against tuberculosis. An experimental outcome was used as a basis to revisit the reverse experimental strategy for tuberculosis management. Stearic mannose was prepared from stearic acid incubation with the D-mannose. Interestingly, stearic mannose explained its internalisation via stimulating actin-mediated phagocytic pathway of MMR experimentally. Following, an in silico strategy towards hypothetical designing of A c c e p t e d M a n u s c r i p t various mannose-stearyl conjugates (SBKK1-7) against tuberculosis, as binding promoter of MMR (PDB: 1EGI), was carried out using molecular docking and dynamics approaches. Overall, SPKK-5 viz. ortho stearic mannose (OSM) showed a higher binding affinity with notable H-bonding and hydrophobic interactions. Pharmacokinetic and toxicity examinations illustrated an ideal range of descriptors values for apex screened compounds. Molecular dynamics simulations have confirmed its significant intactness with the MMR. Ultimately, the whole effort led to the identification of promising hit (SBKK-5), which positively correlates with the experimental work and furthermore need to explore its novel drug delivery systems with improved anti-tubercular therapy.