Malay Kumar Rana - Academia.edu (original) (raw)

Papers by Malay Kumar Rana

Research paper thumbnail of Design, synthesis, antimicrobial activity, DFT, and molecular docking studies of pyridine‐pyrazole‐based dihydro‐1,3,4‐oxadiazoles against various bacterial and fungal targets

Journal of Biochemical and Molecular Toxicology

Research paper thumbnail of Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach

Vaccines

Colorectal cancer (CRC) is one of the most common cancers and is the second-highest in cancer-rel... more Colorectal cancer (CRC) is one of the most common cancers and is the second-highest in cancer-related deaths worldwide. The changes in gut homeostasis and microbial dysbiosis lead to the initiation of the tumorigenesis process. Several pathogenic gram-negative bacteria including Fusobacterium nucleatum are the principal contributors to the induction and pathogenesis of CRC. Thus, inhibiting the growth and survival of these pathogens can be a useful intervention strategy. Fibroblast activation protein-2 (Fap2) is an essential membrane protein of F. nucleatum that promotes the adherence of the bacterium to the colon cells, recruitment of immune cells, and induction of tumorigenesis. The present study depicts the design of an in silico vaccine candidate comprising the B-cell and T-cell epitopes of Fap2 for improving cell-mediated and humoral immune responses against CRC. Notably, this vaccine participates in significant protein–protein interactions with human Toll-like receptors, espec...

Research paper thumbnail of Potential targets of severe acute respiratory syndrome coronavirus 2 of clinical drug fluvoxamine: Docking and molecular dynamics studies to elucidate viral action

Cell Biochemistry and Function

Research paper thumbnail of Simulation study of CO<sub>2</sub> adsorption properties in small Zeolite Imidazolate Frameworks

Applying first principles Born–Oppenheimer Molecular Dynamics and Grand Canonical Monte Carlo sim... more Applying first principles Born–Oppenheimer Molecular Dynamics and Grand Canonical Monte Carlo simulations, we investigated three prototype Zeolite Imidazolate Frameworks to assess the role of their electronic and structural details on CO2 adsorption. We found that the regions proximal to the linkers are the preferential adsorption sites of CO2. The uptake capacity at low pressures is related to the electrostatic interaction of the adsorbate with the crystal. At higher pressures, CO2 adsorption depends linearly on the surface areas and porosities of ZIFs

Research paper thumbnail of Designing efficient multi-epitope peptide-based vaccine by targeting the antioxidant thioredoxin of bancroftian filarial parasite

Infection, Genetics and Evolution, 2022

Thioredoxin is a low molecular weight redox-active protein of filarial parasite that plays a cruc... more Thioredoxin is a low molecular weight redox-active protein of filarial parasite that plays a crucial role in downregulating the host immune response to prolong the survival of the parasite within the host body. It has the ability to cope up with the oxidative challenges posed by the host. Hence, the antioxidant protein of the filarial parasite has been suggested to be a useful target for immunotherapeutic intervention of human filariasis. In this study, we have designed a multi-epitope peptide-based vaccine using thioredoxin of Wuchereria bancrofti. Different MHC-I and MHC-II epitopes were predicted using various web servers to construct the vaccine model as MHC-I and MHC-II epitopes are crucial for the development of both humoral and cellular immune responses. Moreover, TLRs specific adjuvants were also incorporated into the vaccine candidates as TLRs are the key immunomodulator to execute innate immunity. Protein-protein molecular docking and simulation analysis between the vaccine and human TLR was performed. TLR5 is the most potent receptor to convey the vaccine-mediated inductive signal for eliciting an innate immune response. A satisfactory immunogenic report from an in-silico immune simulation experiment directed us to propose our vaccine model for experimental and clinical validation. The reverse translated vaccine sequence was also cloned in pET28a(+) to apply the concept in a wet lab experiment in near future. Taken together, this in-silico study on the design of a vaccine construct to target W. bancrofti thioredoxin is predicted to be a future hope in saving human-being from the threat of filariasis.

Research paper thumbnail of Insights into the Binding Mechanism of Ascorbic Acid and Violaxanthin with Violaxanthin De-Epoxidase (VDE) and Chlorophycean Violaxanthin De-Epoxidase (CVDE) Enzymes: Docking, Molecular Dynamics, and Free Energy Analysis

Photosynthetic organisms have evolved to work under low and high lights in photoprotection, actin... more Photosynthetic organisms have evolved to work under low and high lights in photoprotection, acting as a scavenger of reactive oxygen species. The light dependent xanthophyll cycle involved in this process is performed by a key enzyme (present in the thylakoid lumen) Violaxanthin De-Epoxidase (VDE) in the presence of violaxanthin and ascorbic acid substrates. Phylogenetically, VDE is found to be connected with an ancestral enzyme Chlorophycean Violaxanthin De-Epoxidase (CVDE) present in the green algae on the stromal side of the thylakoid membrane. However, the structure and functions of CVDE were not known. In search of functional similarities involving this cycle, the structure, binding conformation, stability, and interaction mechanism of CVDE are explored with the two substrates in comparison to VDE. The structure of CVDE was determined by homology modeling and validated. In-silico docking (of first-principles-optimized substrates) revealed it has a larger catalytic domain than V...

Research paper thumbnail of Reverse vaccinology assisted design of a novel multi-epitope vaccine to target Wuchereria bancrofti cystatin: An immunoinformatics approach

International Immunopharmacology

Research paper thumbnail of Insights into the binding mechanism of ascorbic acid and violaxanthin with violaxanthin de-epoxidase (VDE) and chlorophycean violaxanthin de-epoxidase (CVDE) enzymes

Research paper thumbnail of α-graphyne as a promising anode material for Na-ion batteries: a first-principles study

Nanotechnology

Lithium-ion batteries (LIBs) have emerged as a technological game-changer. Due to the rising pric... more Lithium-ion batteries (LIBs) have emerged as a technological game-changer. Due to the rising price of lithium and the environmental concerns LIBs pose, their use is no longer viable. Sodium (Na) may be the best contender among the alternatives for replacing lithium. Conventional graphite has a limited capacity for Na storage. Hence, α-graphyne, an allotrope of carbon, was studied here as a potential anode material for Na-ion batteries (NIBs), employing density functional theory. In-plane Na atom adsorption results in a semi-metallic to metallic transition of α-graphyne. Electronic transport calculations show an increase in current after Na adsorption in graphyne. The successive adsorption of Na atoms on the surface of graphyne leads to a theoretical capacity of 1395.89 mA h g−1, which is much greater than graphite. The average open circuit voltage is 0.81 V, which is an ideal operating voltage for NIBs. Intra- and inter-hexagon Na diffusions have very low energy barriers of 0.18 eV ...

Research paper thumbnail of Hydroxyalkynyl uracil derivatives as NNRTIs against HIV-1:in silicopredictions, synthesis, docking and molecular dynamics simulation studies

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of CCDC 1987508: Experimental Crystal Structure Determination

Research paper thumbnail of Designing AbhiSCoVac - A single potential vaccine for all ‘corona culprits’: Immunoinformatics and immune simulation approaches

Journal of Molecular Liquids, 2022

The coronaviridae family has generated highly virulent viruses, including the ones responsible fo... more The coronaviridae family has generated highly virulent viruses, including the ones responsible for three major pandemics in last two decades with SARS in 2002, MERS outbreak in 2012 and the current nCOVID19 crisis that has turned the world breadthless. Future outbreaks are also a plausible threat to mankind. As computational biologists, we are committed to address the need for a universal vaccine that can deter all these pathogenic viruses in a single shot. Notably, the spike proteins present in all these viruses function as credible PAMPs that are majorly sensed by human TLR4 receptors. Our study aims to recognize the amino acid sequence(s) of the viral spike proteins that are precisely responsible for interaction with human TLR4 and to screen the immunogenic epitopes present in them to develop a multi-epitope multi-target chimeric vaccine against the coronaviruses. Molecular design of the constructed vaccine peptide is qualified in silico; additionally, molecular docking and molecular dynamics simulation studies collectively reveal strong and stable interactions of the vaccine construct with TLRs and MHC receptors. In silico cloning is performed for proficient expression in bacterial systems. In silico immune simulation of the vaccine indicates highly immunogenic nature of the vaccine construct without any allergic response. The present biocomputational study hereby innovates a vaccine candidate - AbhiSCoVac hypothesized as a potent remedy to combat all the virulent forms of coronaviruses.

Research paper thumbnail of Repurposing of FDA-approved drugs as potential inhibitors of the SARS-CoV-2 main protease: Molecular insights into improved therapeutic discovery

Computers in Biology and Medicine, 2021

With numerous infections and fatalities, COVID-19 has wreaked havoc around the globe. The main pr... more With numerous infections and fatalities, COVID-19 has wreaked havoc around the globe. The main protease (Mpro), which cleaves the polyprotein to form non-structural proteins, thereby helping in the replication of SARS-CoV-2, appears as an attractive target for antiviral therapeutics. As FDA-approved drugs have shown effectiveness in targeting Mpro in previous SARS-CoV(s), molecular docking and virtual screening of existing antiviral, antimalarial, and protease inhibitor drugs were carried out against SARS-CoV-2 Mpro. Among 53 shortlisted drugs with binding energies lower than that of the crystal-bound inhibitor α-ketoamide 13 b (−6.7 kcal/mol), velpatasvir, glecaprevir, grazoprevir, baloxavir marboxil, danoprevir, nelfinavir, and indinavir (−9.1 to −7.5 kcal/mol) were the most significant on the list (hereafter referred to as the 53-list). Molecular dynamics (MD) simulations confirmed the stability of their Mpro complexes, with the MMPBSA binding free energy (ΔGbind) ranging between −124 kJ/mol (glecaprevir) and −28.2 kJ/mol (velpatasvir). Despite having the lowest initial binding energy, velpatasvir exhibited the highest ΔGbind value for escaping the catalytic site during the MD simulations, indicating its reduced efficacy, as observed experimentally. Available inhibition assay data adequately substantiated the computational forecast. Glecaprevir and nelfinavir (ΔGbind = −95.4 kJ/mol) appear to be the most effective antiviral drugs against Mpro. Furthermore, the remaining FDA drugs on the 53-list can be worth considering, since some have already demonstrated antiviral activity against SARS-CoV-2. Hence, theoretical pKi (Ki = inhibitor constant) values for all 53 drugs were provided. Notably, ΔGbind directly correlates with the average distance of the drugs from the His41–Cys145 catalytic dyad of Mpro, providing a roadmap for rapid screening and improving the inhibitor design against SARS-CoV-2 Mpro.

Research paper thumbnail of A “Thermodynamically Stable” 2D Nickel Metal–Organic Framework over a Wide pH Range with Scalable Preparation for Efficient C 2 s over C 1 Hydrocarbon Separations

Chemistry – A European Journal, 2020

Design and construction of 'thermodynamically stable' MOFs surviving in liquid water, boi... more Design and construction of 'thermodynamically stable' MOFs surviving in liquid water, boiling water, acidic/basic solutions over a wide pH range is highly desirable for many practical applications especially adsorption based gas separations with obvious scalable preparations. Herein, we have designed a new thermodynamically stable Ni-MOF, {[Ni(L)(1,4-NDC)(H 2 O) 2 ]} n , IITKGP-20 displaying moderate porosity with 218 m 2 g -1 BET surface area and micropores along [1 0 -1] direction. As an alternate to cost intensive cryogenic high pressure distillation process for the separation of hydrocarbons, recently MOFs have shown the promise of such separation. Thus, towards application standpoint, this MOF exhibits relatively higher uptake of C 2 s hydrocarbons over the C 1 hydrocarbon at ambient conditions with one of the highest selectivities based on IAST method. Combination of two strategies (presence of stronger metal-N coordination on the spacer and the hydrophobicity on the aromatic moiety of the organic ligand) possibly makes the framework highly robust even stable in boiling water and over a wide range of pH 2-10 and representing the first example of 'thermodynamically stable' MOF displaying 2D structural network. Moreover, this material is easily scalable by refluxing the reaction mixture overnight. Because, such separations are performed in presence of water vapor and acidic gases, there is a great need to explore 'thermodynamically stable' MOFs retaining not only the structural integrity but also the porosity of frameworks.

Research paper thumbnail of Binding insight of clinically oriented drug famotidine with the identified potential target of SARS-CoV-2

Journal of Biomolecular Structure and Dynamics, 2020

Research paper thumbnail of Anion Sensing by Novel Triarylboranes Containing Boraanthracene: DFT Functional Assessment, Selective Interactions, and Mechanism Demonstration

ACS Omega, 2019

Analytical methods often involve expensive instrumentation and tedious sample pretreatment for an... more Analytical methods often involve expensive instrumentation and tedious sample pretreatment for an analyte detection. Being toxic and detrimental to human health, sensing of cyanide (CN −), fluoride (F −), chloride (Cl −), bromide (Br −), nitrate (NO 3 −), acetate (CH 3 COO −), and bisulfate (HSO 4 −) is performed by a boron-based molecular receptor, N,N,N,3,5-pentamethyl-4-{2-thia-9boratricyclo[8.4.0.0 3,8 ]tetradeca-1(10),3(8),4,6,11,13-hexaen-9-yl}anili-nium (1), and the three newly designed receptors from it. Thermodynamics, electronic structure, and photophysical properties are computed by employing density functional theory (DFT) and time-dependent density functional theory (TD-DFT) to explore selective sensing of these anions and its mechanism. Free-energy changes (ΔG) and binding energies (ΔE) suggest that among these anions, only binding of CN − and F − is thermodynamically feasible with a very strong binding affinity with the receptors. Boron atoms containing positive natural charges act as the electrophilic centers to bind the anions involving a 2p−2p orbital overlap resulting in charge transfer. In the receptor−analyte complexes with CN − and F − , fluorescence is quenched due to the intramolecular charge transfer transitions (π−π* transitions in the case of the receptors lead to fluorescence), internal conversion, and associated configurational changes. Among the six tested functionals, CAM-B3LYP/6-31G(d) is found to be the most accurate one. The designed receptors are better fluorescent probes for F − and CN − , demonstrating their importance for the practical utility.

Research paper thumbnail of Solvation of narrow pores of graphene-like plates in simple dipolar liquids: Wetting and dewetting behavior and solvent dynamics for varying pore width and solute–solvent interaction

Chemical Physics, 2015

Abstract We have investigated the solvation behavior of two parallel graphene-like plates in a St... more Abstract We have investigated the solvation behavior of two parallel graphene-like plates in a Stockmayer liquid by molecular dynamics simulations for varying inter-plate separation and plate–solvent interactions. The solvent structure, orientation and dynamics around the plates and in their confined pores have been calculated. Layering of Stockmayer molecules with dipole vectors parallel to the surfaces is observed in the vicinity of the nonpolar plates. Density profiles reveal wetting and emptying of the narrow pores depending on the nature of solute–solvent interactions. In the interior and outer surface regions, solvent molecules are found to exhibit a significantly different dynamics than the bulk. From an overall perspective, the solvophobic effects observed here can be considered as the generic behavior of dipolar liquids near nonpolar surfaces without the presence of any specific and complex intermolecular interactions such as hydrogen bonds in water and other protic solvents.

Research paper thumbnail of Filled and empty states of carbon nanotubes in water: Dependence on nanotube diameter, wall thickness and dispersion interactions

Journal of Chemical Sciences, 2007

We have carried out a series of molecular dynamics simulations of water containing a narrow carbo... more We have carried out a series of molecular dynamics simulations of water containing a narrow carbon nanotube as a solute to investigate the filling and emptying of the nanotube and also the modifications of the density and hydrogen bond distributions of water inside and also in the vicinity of the outer surfaces of the nanotube. Our primary goal is to look at the effects of varying nanotube diameter, wall thickness and also solute-solvent interactions on the solvent structure in the confined region also near the outer surfaces of the solute. The thickness of the walls is varied by considering single and multi-walled nanotubes and the interaction potential is varied by tuning the attractive strength of the 12-6 pair interaction potential between a carbon atom of the nanotubes and a water molecule. The calculations are done for many different values of the tuning parameter ranging from fully Lennard-Jones to pure repulsive pair interactions. It is found that both the solvation characteristics and hydrogen bond distributions can depend rather strongly on the strength of the attractive part of the solute-water interaction potential. The thickness of the nanotube wall, however, is found to have only minor effects on the density profiles, hydrogen bond network and the wetting characteristics. This indicates that the long range electrostatic interactions between water molecules inside and on the outer side of the nanotube do not make any significant contribution to the overall solvation structure of these hydrophobic solutes. The solvation characteristics are primarily determined by the balance between the loss of energy due to hydrogen bond network disruption, cavity repulsion potential and offset of the same by attractive component of the solute-water interactions. Our studies with different system sizes show that the essential features of wetting and dewetting characteristics of narrow nanotubes for different diameter and interaction potentials are also present in relatively smaller systems consisting of about five hundred molecules.

Research paper thumbnail of Ab initio and classical molecular dynamics studies of electrode reactions

Electrochimica Acta, 2003

ABSTRACT

Research paper thumbnail of Screening and molecular characterization of lethal mutations of human homogentisate 1, 2 dioxigenase

Journal of Biomolecular Structure and Dynamics, 2020

Alkaptonuria (AKU) is an autosomal recessive disorder, which is caused by a site-specific mutatio... more Alkaptonuria (AKU) is an autosomal recessive disorder, which is caused by a site-specific mutation(s) and thus, impaired the function of Homogentisate-1, 2-dioxygenase (HGD), an essential enzyme for the catabolism of phenylalanine and tyrosine. Among frameshift, intronic, splice-site and missense mutations, the latter has been the most common form of genetic variations for the disease. How do the acquired mutations in HGD correlate with the disease? Systematic staged-screening of some sixty-five mutations, which are known to have a relation with the disease, by GVGD, SIFT, SNAP, PANTHER, SDM, PHD-SNP, Meta-SNP, Pmut and Mutpred methods, showed that mutations, W60G, A122D and V300G are potentially related with the severity of AKU. Detailed analyses on molecular docking and molecular dynamics simulation (MDS) of these mutants against the wild-type HGD reveal the loss of structural and molecular dynamic properties of the enzyme. Further, the observed conformational flexibility in mutants at targeted peptide segments seems to have a relation with the impairment of the function of HGD. Taken together, the study involves designed computational methodology to A c c e p t e d M a n u s c r i p t 2 analyses the disease-associated nsSNPs for AKU, the knowledge of which seem to have potential applications in drug therapies for the disease in particular and other similar systems in general.

Research paper thumbnail of Design, synthesis, antimicrobial activity, DFT, and molecular docking studies of pyridine‐pyrazole‐based dihydro‐1,3,4‐oxadiazoles against various bacterial and fungal targets

Journal of Biochemical and Molecular Toxicology

Research paper thumbnail of Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach

Vaccines

Colorectal cancer (CRC) is one of the most common cancers and is the second-highest in cancer-rel... more Colorectal cancer (CRC) is one of the most common cancers and is the second-highest in cancer-related deaths worldwide. The changes in gut homeostasis and microbial dysbiosis lead to the initiation of the tumorigenesis process. Several pathogenic gram-negative bacteria including Fusobacterium nucleatum are the principal contributors to the induction and pathogenesis of CRC. Thus, inhibiting the growth and survival of these pathogens can be a useful intervention strategy. Fibroblast activation protein-2 (Fap2) is an essential membrane protein of F. nucleatum that promotes the adherence of the bacterium to the colon cells, recruitment of immune cells, and induction of tumorigenesis. The present study depicts the design of an in silico vaccine candidate comprising the B-cell and T-cell epitopes of Fap2 for improving cell-mediated and humoral immune responses against CRC. Notably, this vaccine participates in significant protein–protein interactions with human Toll-like receptors, espec...

Research paper thumbnail of Potential targets of severe acute respiratory syndrome coronavirus 2 of clinical drug fluvoxamine: Docking and molecular dynamics studies to elucidate viral action

Cell Biochemistry and Function

Research paper thumbnail of Simulation study of CO<sub>2</sub> adsorption properties in small Zeolite Imidazolate Frameworks

Applying first principles Born–Oppenheimer Molecular Dynamics and Grand Canonical Monte Carlo sim... more Applying first principles Born–Oppenheimer Molecular Dynamics and Grand Canonical Monte Carlo simulations, we investigated three prototype Zeolite Imidazolate Frameworks to assess the role of their electronic and structural details on CO2 adsorption. We found that the regions proximal to the linkers are the preferential adsorption sites of CO2. The uptake capacity at low pressures is related to the electrostatic interaction of the adsorbate with the crystal. At higher pressures, CO2 adsorption depends linearly on the surface areas and porosities of ZIFs

Research paper thumbnail of Designing efficient multi-epitope peptide-based vaccine by targeting the antioxidant thioredoxin of bancroftian filarial parasite

Infection, Genetics and Evolution, 2022

Thioredoxin is a low molecular weight redox-active protein of filarial parasite that plays a cruc... more Thioredoxin is a low molecular weight redox-active protein of filarial parasite that plays a crucial role in downregulating the host immune response to prolong the survival of the parasite within the host body. It has the ability to cope up with the oxidative challenges posed by the host. Hence, the antioxidant protein of the filarial parasite has been suggested to be a useful target for immunotherapeutic intervention of human filariasis. In this study, we have designed a multi-epitope peptide-based vaccine using thioredoxin of Wuchereria bancrofti. Different MHC-I and MHC-II epitopes were predicted using various web servers to construct the vaccine model as MHC-I and MHC-II epitopes are crucial for the development of both humoral and cellular immune responses. Moreover, TLRs specific adjuvants were also incorporated into the vaccine candidates as TLRs are the key immunomodulator to execute innate immunity. Protein-protein molecular docking and simulation analysis between the vaccine and human TLR was performed. TLR5 is the most potent receptor to convey the vaccine-mediated inductive signal for eliciting an innate immune response. A satisfactory immunogenic report from an in-silico immune simulation experiment directed us to propose our vaccine model for experimental and clinical validation. The reverse translated vaccine sequence was also cloned in pET28a(+) to apply the concept in a wet lab experiment in near future. Taken together, this in-silico study on the design of a vaccine construct to target W. bancrofti thioredoxin is predicted to be a future hope in saving human-being from the threat of filariasis.

Research paper thumbnail of Insights into the Binding Mechanism of Ascorbic Acid and Violaxanthin with Violaxanthin De-Epoxidase (VDE) and Chlorophycean Violaxanthin De-Epoxidase (CVDE) Enzymes: Docking, Molecular Dynamics, and Free Energy Analysis

Photosynthetic organisms have evolved to work under low and high lights in photoprotection, actin... more Photosynthetic organisms have evolved to work under low and high lights in photoprotection, acting as a scavenger of reactive oxygen species. The light dependent xanthophyll cycle involved in this process is performed by a key enzyme (present in the thylakoid lumen) Violaxanthin De-Epoxidase (VDE) in the presence of violaxanthin and ascorbic acid substrates. Phylogenetically, VDE is found to be connected with an ancestral enzyme Chlorophycean Violaxanthin De-Epoxidase (CVDE) present in the green algae on the stromal side of the thylakoid membrane. However, the structure and functions of CVDE were not known. In search of functional similarities involving this cycle, the structure, binding conformation, stability, and interaction mechanism of CVDE are explored with the two substrates in comparison to VDE. The structure of CVDE was determined by homology modeling and validated. In-silico docking (of first-principles-optimized substrates) revealed it has a larger catalytic domain than V...

Research paper thumbnail of Reverse vaccinology assisted design of a novel multi-epitope vaccine to target Wuchereria bancrofti cystatin: An immunoinformatics approach

International Immunopharmacology

Research paper thumbnail of Insights into the binding mechanism of ascorbic acid and violaxanthin with violaxanthin de-epoxidase (VDE) and chlorophycean violaxanthin de-epoxidase (CVDE) enzymes

Research paper thumbnail of α-graphyne as a promising anode material for Na-ion batteries: a first-principles study

Nanotechnology

Lithium-ion batteries (LIBs) have emerged as a technological game-changer. Due to the rising pric... more Lithium-ion batteries (LIBs) have emerged as a technological game-changer. Due to the rising price of lithium and the environmental concerns LIBs pose, their use is no longer viable. Sodium (Na) may be the best contender among the alternatives for replacing lithium. Conventional graphite has a limited capacity for Na storage. Hence, α-graphyne, an allotrope of carbon, was studied here as a potential anode material for Na-ion batteries (NIBs), employing density functional theory. In-plane Na atom adsorption results in a semi-metallic to metallic transition of α-graphyne. Electronic transport calculations show an increase in current after Na adsorption in graphyne. The successive adsorption of Na atoms on the surface of graphyne leads to a theoretical capacity of 1395.89 mA h g−1, which is much greater than graphite. The average open circuit voltage is 0.81 V, which is an ideal operating voltage for NIBs. Intra- and inter-hexagon Na diffusions have very low energy barriers of 0.18 eV ...

Research paper thumbnail of Hydroxyalkynyl uracil derivatives as NNRTIs against HIV-1:in silicopredictions, synthesis, docking and molecular dynamics simulation studies

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of CCDC 1987508: Experimental Crystal Structure Determination

Research paper thumbnail of Designing AbhiSCoVac - A single potential vaccine for all ‘corona culprits’: Immunoinformatics and immune simulation approaches

Journal of Molecular Liquids, 2022

The coronaviridae family has generated highly virulent viruses, including the ones responsible fo... more The coronaviridae family has generated highly virulent viruses, including the ones responsible for three major pandemics in last two decades with SARS in 2002, MERS outbreak in 2012 and the current nCOVID19 crisis that has turned the world breadthless. Future outbreaks are also a plausible threat to mankind. As computational biologists, we are committed to address the need for a universal vaccine that can deter all these pathogenic viruses in a single shot. Notably, the spike proteins present in all these viruses function as credible PAMPs that are majorly sensed by human TLR4 receptors. Our study aims to recognize the amino acid sequence(s) of the viral spike proteins that are precisely responsible for interaction with human TLR4 and to screen the immunogenic epitopes present in them to develop a multi-epitope multi-target chimeric vaccine against the coronaviruses. Molecular design of the constructed vaccine peptide is qualified in silico; additionally, molecular docking and molecular dynamics simulation studies collectively reveal strong and stable interactions of the vaccine construct with TLRs and MHC receptors. In silico cloning is performed for proficient expression in bacterial systems. In silico immune simulation of the vaccine indicates highly immunogenic nature of the vaccine construct without any allergic response. The present biocomputational study hereby innovates a vaccine candidate - AbhiSCoVac hypothesized as a potent remedy to combat all the virulent forms of coronaviruses.

Research paper thumbnail of Repurposing of FDA-approved drugs as potential inhibitors of the SARS-CoV-2 main protease: Molecular insights into improved therapeutic discovery

Computers in Biology and Medicine, 2021

With numerous infections and fatalities, COVID-19 has wreaked havoc around the globe. The main pr... more With numerous infections and fatalities, COVID-19 has wreaked havoc around the globe. The main protease (Mpro), which cleaves the polyprotein to form non-structural proteins, thereby helping in the replication of SARS-CoV-2, appears as an attractive target for antiviral therapeutics. As FDA-approved drugs have shown effectiveness in targeting Mpro in previous SARS-CoV(s), molecular docking and virtual screening of existing antiviral, antimalarial, and protease inhibitor drugs were carried out against SARS-CoV-2 Mpro. Among 53 shortlisted drugs with binding energies lower than that of the crystal-bound inhibitor α-ketoamide 13 b (−6.7 kcal/mol), velpatasvir, glecaprevir, grazoprevir, baloxavir marboxil, danoprevir, nelfinavir, and indinavir (−9.1 to −7.5 kcal/mol) were the most significant on the list (hereafter referred to as the 53-list). Molecular dynamics (MD) simulations confirmed the stability of their Mpro complexes, with the MMPBSA binding free energy (ΔGbind) ranging between −124 kJ/mol (glecaprevir) and −28.2 kJ/mol (velpatasvir). Despite having the lowest initial binding energy, velpatasvir exhibited the highest ΔGbind value for escaping the catalytic site during the MD simulations, indicating its reduced efficacy, as observed experimentally. Available inhibition assay data adequately substantiated the computational forecast. Glecaprevir and nelfinavir (ΔGbind = −95.4 kJ/mol) appear to be the most effective antiviral drugs against Mpro. Furthermore, the remaining FDA drugs on the 53-list can be worth considering, since some have already demonstrated antiviral activity against SARS-CoV-2. Hence, theoretical pKi (Ki = inhibitor constant) values for all 53 drugs were provided. Notably, ΔGbind directly correlates with the average distance of the drugs from the His41–Cys145 catalytic dyad of Mpro, providing a roadmap for rapid screening and improving the inhibitor design against SARS-CoV-2 Mpro.

Research paper thumbnail of A “Thermodynamically Stable” 2D Nickel Metal–Organic Framework over a Wide pH Range with Scalable Preparation for Efficient C 2 s over C 1 Hydrocarbon Separations

Chemistry – A European Journal, 2020

Design and construction of 'thermodynamically stable' MOFs surviving in liquid water, boi... more Design and construction of 'thermodynamically stable' MOFs surviving in liquid water, boiling water, acidic/basic solutions over a wide pH range is highly desirable for many practical applications especially adsorption based gas separations with obvious scalable preparations. Herein, we have designed a new thermodynamically stable Ni-MOF, {[Ni(L)(1,4-NDC)(H 2 O) 2 ]} n , IITKGP-20 displaying moderate porosity with 218 m 2 g -1 BET surface area and micropores along [1 0 -1] direction. As an alternate to cost intensive cryogenic high pressure distillation process for the separation of hydrocarbons, recently MOFs have shown the promise of such separation. Thus, towards application standpoint, this MOF exhibits relatively higher uptake of C 2 s hydrocarbons over the C 1 hydrocarbon at ambient conditions with one of the highest selectivities based on IAST method. Combination of two strategies (presence of stronger metal-N coordination on the spacer and the hydrophobicity on the aromatic moiety of the organic ligand) possibly makes the framework highly robust even stable in boiling water and over a wide range of pH 2-10 and representing the first example of 'thermodynamically stable' MOF displaying 2D structural network. Moreover, this material is easily scalable by refluxing the reaction mixture overnight. Because, such separations are performed in presence of water vapor and acidic gases, there is a great need to explore 'thermodynamically stable' MOFs retaining not only the structural integrity but also the porosity of frameworks.

Research paper thumbnail of Binding insight of clinically oriented drug famotidine with the identified potential target of SARS-CoV-2

Journal of Biomolecular Structure and Dynamics, 2020

Research paper thumbnail of Anion Sensing by Novel Triarylboranes Containing Boraanthracene: DFT Functional Assessment, Selective Interactions, and Mechanism Demonstration

ACS Omega, 2019

Analytical methods often involve expensive instrumentation and tedious sample pretreatment for an... more Analytical methods often involve expensive instrumentation and tedious sample pretreatment for an analyte detection. Being toxic and detrimental to human health, sensing of cyanide (CN −), fluoride (F −), chloride (Cl −), bromide (Br −), nitrate (NO 3 −), acetate (CH 3 COO −), and bisulfate (HSO 4 −) is performed by a boron-based molecular receptor, N,N,N,3,5-pentamethyl-4-{2-thia-9boratricyclo[8.4.0.0 3,8 ]tetradeca-1(10),3(8),4,6,11,13-hexaen-9-yl}anili-nium (1), and the three newly designed receptors from it. Thermodynamics, electronic structure, and photophysical properties are computed by employing density functional theory (DFT) and time-dependent density functional theory (TD-DFT) to explore selective sensing of these anions and its mechanism. Free-energy changes (ΔG) and binding energies (ΔE) suggest that among these anions, only binding of CN − and F − is thermodynamically feasible with a very strong binding affinity with the receptors. Boron atoms containing positive natural charges act as the electrophilic centers to bind the anions involving a 2p−2p orbital overlap resulting in charge transfer. In the receptor−analyte complexes with CN − and F − , fluorescence is quenched due to the intramolecular charge transfer transitions (π−π* transitions in the case of the receptors lead to fluorescence), internal conversion, and associated configurational changes. Among the six tested functionals, CAM-B3LYP/6-31G(d) is found to be the most accurate one. The designed receptors are better fluorescent probes for F − and CN − , demonstrating their importance for the practical utility.

Research paper thumbnail of Solvation of narrow pores of graphene-like plates in simple dipolar liquids: Wetting and dewetting behavior and solvent dynamics for varying pore width and solute–solvent interaction

Chemical Physics, 2015

Abstract We have investigated the solvation behavior of two parallel graphene-like plates in a St... more Abstract We have investigated the solvation behavior of two parallel graphene-like plates in a Stockmayer liquid by molecular dynamics simulations for varying inter-plate separation and plate–solvent interactions. The solvent structure, orientation and dynamics around the plates and in their confined pores have been calculated. Layering of Stockmayer molecules with dipole vectors parallel to the surfaces is observed in the vicinity of the nonpolar plates. Density profiles reveal wetting and emptying of the narrow pores depending on the nature of solute–solvent interactions. In the interior and outer surface regions, solvent molecules are found to exhibit a significantly different dynamics than the bulk. From an overall perspective, the solvophobic effects observed here can be considered as the generic behavior of dipolar liquids near nonpolar surfaces without the presence of any specific and complex intermolecular interactions such as hydrogen bonds in water and other protic solvents.

Research paper thumbnail of Filled and empty states of carbon nanotubes in water: Dependence on nanotube diameter, wall thickness and dispersion interactions

Journal of Chemical Sciences, 2007

We have carried out a series of molecular dynamics simulations of water containing a narrow carbo... more We have carried out a series of molecular dynamics simulations of water containing a narrow carbon nanotube as a solute to investigate the filling and emptying of the nanotube and also the modifications of the density and hydrogen bond distributions of water inside and also in the vicinity of the outer surfaces of the nanotube. Our primary goal is to look at the effects of varying nanotube diameter, wall thickness and also solute-solvent interactions on the solvent structure in the confined region also near the outer surfaces of the solute. The thickness of the walls is varied by considering single and multi-walled nanotubes and the interaction potential is varied by tuning the attractive strength of the 12-6 pair interaction potential between a carbon atom of the nanotubes and a water molecule. The calculations are done for many different values of the tuning parameter ranging from fully Lennard-Jones to pure repulsive pair interactions. It is found that both the solvation characteristics and hydrogen bond distributions can depend rather strongly on the strength of the attractive part of the solute-water interaction potential. The thickness of the nanotube wall, however, is found to have only minor effects on the density profiles, hydrogen bond network and the wetting characteristics. This indicates that the long range electrostatic interactions between water molecules inside and on the outer side of the nanotube do not make any significant contribution to the overall solvation structure of these hydrophobic solutes. The solvation characteristics are primarily determined by the balance between the loss of energy due to hydrogen bond network disruption, cavity repulsion potential and offset of the same by attractive component of the solute-water interactions. Our studies with different system sizes show that the essential features of wetting and dewetting characteristics of narrow nanotubes for different diameter and interaction potentials are also present in relatively smaller systems consisting of about five hundred molecules.

Research paper thumbnail of Ab initio and classical molecular dynamics studies of electrode reactions

Electrochimica Acta, 2003

ABSTRACT

Research paper thumbnail of Screening and molecular characterization of lethal mutations of human homogentisate 1, 2 dioxigenase

Journal of Biomolecular Structure and Dynamics, 2020

Alkaptonuria (AKU) is an autosomal recessive disorder, which is caused by a site-specific mutatio... more Alkaptonuria (AKU) is an autosomal recessive disorder, which is caused by a site-specific mutation(s) and thus, impaired the function of Homogentisate-1, 2-dioxygenase (HGD), an essential enzyme for the catabolism of phenylalanine and tyrosine. Among frameshift, intronic, splice-site and missense mutations, the latter has been the most common form of genetic variations for the disease. How do the acquired mutations in HGD correlate with the disease? Systematic staged-screening of some sixty-five mutations, which are known to have a relation with the disease, by GVGD, SIFT, SNAP, PANTHER, SDM, PHD-SNP, Meta-SNP, Pmut and Mutpred methods, showed that mutations, W60G, A122D and V300G are potentially related with the severity of AKU. Detailed analyses on molecular docking and molecular dynamics simulation (MDS) of these mutants against the wild-type HGD reveal the loss of structural and molecular dynamic properties of the enzyme. Further, the observed conformational flexibility in mutants at targeted peptide segments seems to have a relation with the impairment of the function of HGD. Taken together, the study involves designed computational methodology to A c c e p t e d M a n u s c r i p t 2 analyses the disease-associated nsSNPs for AKU, the knowledge of which seem to have potential applications in drug therapies for the disease in particular and other similar systems in general.