Epidermal growth factor receptor tyrosine kinase domain (EGFR-TKD) plays a pivotal role in cellul... more Epidermal growth factor receptor tyrosine kinase domain (EGFR-TKD) plays a pivotal role in cellular signaling, growth, and metabolism. The EGFR-TKD is highly expressed in cancer cells and was endorsed as a therapeutic target for cancer management to overcome metastasis, cell proliferation, and angiogenesis. The novel thiazolo-[2,3-b]quinazolinones series were strategically developed by microwave-assisted organic synthesis and multi dominos reactions aimed to identify the potent thiazolo-[2,3-b]quinazolinone inhibitor against EGFR-TKD. This study explores the binding stability and binding strength of newly developed series via molecular docking, molecular dynamics simulation, and MM/ PBSA and MM/GBSA calculations. The binding interaction was observed to be through the functional groups on aryl substituents at positions 3 and 5 of the thiazolo-[2, 3-b] quinazolinone scaffold. The methyl substituents at position 8 of the ligands had prominent hydrophobic interactions corroborating their bindings similar to the reference FDAapproved drug erlotinib in the active site. ADMET predictions reveal that derivatives 5ab, 5aq, and 5bq are drug-like and may be effective in in vitro study. Molecular dynamics simulation for 100 ns of docked complexes revealed their stability at the atomistic level. The ΔGbinding of thiazolo-[2,3-b]quinazolinone was found to be 5ab − 22.45, 5aq − 22.23, and 5bq − 20.76 similar to standard drug, and erlotinib − 24.11 kcal/mol was determined by MM/GBSA method. Furthermore, the anti-proliferative activity of leads of thiazolo-[2,3b]quinazolinones (n = 3) was studied against breast cancer cell line (MCF-7) and nonsmall lung carcinoma cell line (H-1299). The highest inhibitions in cell proliferation were shown by 5bq derivatives, and the IC 50 was found to be 6.5 ± 0.67 µM against MCF-7 and 14.8 µM against H-1299. The noscapine was also taken as a positive control and showed IC 50 at higher concentrations 37 ± 1 against MCF-7 and 46.5 ± 1.2 against H-1299.
Chloroplast development describes the life cycle of plastids from the proplastid to the mature ch... more Chloroplast development describes the life cycle of plastids from the proplastid to the mature chloroplast, which is subsequently transformed to a gerontoplast and finally to a necrotic plastid. Similar to any living system, the chloroplast may be defined as an open thermodynamic system far away from equilibrium. It has self-organized dissipative structures, namely, metabolome and genome, which fluctuate with development. The proplastid grows to become a mature chloroplast with self-organizing metabolic networks consisting of core, plastic, and signaling subsystems. The major function of the chloroplast is photosynthesis. Light induces redox reactions resulting finally into the synthesis of sugars. The photoelectron transport systems and sugars are not only two components of the core metabolic network, but these are also elements of signaling subsystems. The signaling regulatory and metabolic networks associated with chloroplast development are complex in nature and therefore are not fully understood. Many experimental data in the area remain to be explained without ambiguity. Examination of chloroplast development with respect to time, structure and fluctuations under the lens of non-equilibrium thermodynamics may contribute to our understanding of the process.
The transformations of proplastid to chloroplast and subsequently chloroplast to gerontoplast are... more The transformations of proplastid to chloroplast and subsequently chloroplast to gerontoplast are tightly coupled to the leaf development. The assembly and organization of chloroplast occur during leaf growth and expansion whereas the process of disassembly of the organelle starts when leaf turns yellow during senescence. Both assembly and disassembly processes are controlled by several factors with active participation of both plastid and nuclear genes. In both the cases the nuclear genome plays a major regulatory role although the role of a plastid factor in controlling some of the events has been suggested.
Zenodo (CERN European Organization for Nuclear Research), Mar 31, 1995
Schiff bases derived from 4,4'-diaminodiphenylsulphone with salicyladehyde and 2-hydroxy-1-naphth... more Schiff bases derived from 4,4'-diaminodiphenylsulphone with salicyladehyde and 2-hydroxy-1-naphthaldehyde behave as ON-x-NO donor doubl("bidentate ligands and form dinuclear complexes with divalent Co, Ni, Cu, Zn, Cd and Hg ions. The Co 1 , Ni 11 and Cuu complexes are found to be either octahedral or distorted-octahedral, whereas a tetradedral stereochemistry can be assigned to the Zn 11 , Cd 11 and Hg 11 complexes. The complexes have been characterised by analytical, conductance, magnetic, ir, electronic, esr and nmr spectral data.
Received 01 September 2014; accepted 10 September 2014 Abstract The kinks (bends) in helices play... more Received 01 September 2014; accepted 10 September 2014 Abstract The kinks (bends) in helices play an important role in functions of transmembrane proteins. Kinked helices are believed to be required for appropriate helix-helix and protein-protein interaction in membrane protein complexes. Therefore, knowledge of kink and its prediction from amino acid sequences is of great help in understanding the function of proteins. However, determination of kink in transmembrane α-helices is a computationally intensive task. In this paper we have developed Neural Network method based on radial basis function for prediction of kink in the helices with a prediction efficiency of 85%. A feature vector generated using three physico-chemical properties such as alpha propensity, coil propensity, and EIIP constituted in kinked helices contains most of the necessary information in determining the kink location. The proposed method captures this information more effectively than existing methods. Keywords Kink, Transmembrane α-helices, RBF, Feature vector, Physico-chemical properties. Knowledge of segments of transmembrane proteins and the bends in helices help in the study of tertiary structure and hence understanding the role played by that protein. 20-30% of all the proteins in any organism are membrane proteins. These are of particular importance because they form targets for over 60% of drugs on the market. Transmembrane α-helix bundle is a common structural feature of membrane proteins except porins, which contains β-barrels. Membrane spanning α-helices differ from their globular counterpart by the presence of helix breakers, Pro and Gly, in the middle of helices. Pro is known to induce a kink in the helix 1,2 . A hypothesis suggests that Pro is
Background: Harvesting solar energy through artificial photosynthetic device is gaining momentum ... more Background: Harvesting solar energy through artificial photosynthetic device is gaining momentum in the present era. Artificial photosynthetic device is a promising solution to the energy crisis by overcoming the crunch in fossil fuel and low efficiency of heat engine. Objective: An attempt has been made to design in silico an artificial photoreaction center mimicking the photosynthetic reaction center II. Method: A closely packed transmembrane four helix bundle protein with all the helices interacting with one another (PDB ID 2bl2) is selected for the purpose. The protein is suitably mutated in silico to accommodate the basic elements of a reaction center: oxidizing moiety, reducing moiety and photosensitizerto achieve the desired function of photo-redox reaction. Results: A model has been built. The transmembrane orientation in the artificial membrane system and energetic feasibility of photoredox reaction of the molecular device has been validated theoretically. Conclusion: A syn...
Objective: Lysin specific demethylase 1 (LSD1) inhibits the tumor suppressor activity of p53 and ... more Objective: Lysin specific demethylase 1 (LSD1) inhibits the tumor suppressor activity of p53 and facilitates the progress of tumor. In order to check the tumor growth, the activity of LSD1 enzyme is to be blunted.Methods: Phytochemicals from naturally occurring plant-based anti-cancer compound-activity-target (NPACT) database are screened with LSD1 as target applying genetic algorithm (GA) method to study best ligand poses and free energy of binding using Argus Lab. The prediction of drug-likeness and oral toxicity of the ligands are performed by the online tools Molsoft and ProTox respectively.Results: Calyxin H shows optimum binding affinity to both the substrate and FAD binding sites of LSD1. The LD50 value (median lethal dose) of calyxin H is more than 1000 mg/kg body weight and the toxicity class is 4.Conclusions: Calyxin H is the inhibitor of choice against target LSD1. The lead molecule may be the future potential herbal drug for cancer treatment.
The 33 kD extrinsic polypeptide binds to D1 and D2 polypeptides of reaction center II (RC II) of ... more The 33 kD extrinsic polypeptide binds to D1 and D2 polypeptides of reaction center II (RC II) of thylakoid from the lumen side (1–3). The pKa value of the polypeptide is reported to be 5.2 (4). The nature of binding of the 33 kD polypeptide to D1/D2 or membrane is not established. However, the polypeptide dissociates from its binding site by Ca2+, tris washing, heat treatment and high pH, but it does not dissociate by NaCl washing (5). Further, the polypeptide is reported to (i) regulate S3 → S0 transition of oxygen evolving system (6) (ii) maintain the conformation of oxygen evolving complex (7) (iii) stabilize Mn associated with oxygen evolution (5) (iv) accumulate Cl− required for oxygen evolution (5) and (v) have Mn—oxidase activity (8).
A model for the oxidation of water in chloroplasts is suggested. This model is based on certain p... more A model for the oxidation of water in chloroplasts is suggested. This model is based on certain physico-chemical principles and it accommodates the experimental results associated with the O,-evolving system. The model consists of two pools of heterogeneously bound manganese. Two manganese ions are bound to an enzyme system containing a water-splitting site and four manganese ions are bound to another protein system which connects the reaction centre of photosystem II to the water-splitting enzyme. The latter pool of manganese acts as an electron carrier and an electron trap. It is proposed that water is oxidised in the enzyme system to form H202 and 0; as transient species, and finally liberates 0,. This pathway is energetically feasible. The model explains the flash yield kinetics of O,-evolution and the action of various artificial electron donors and inhibitors of photosystem II. It gives a molecular picture and the quantum requirements of the redox reactions associated with the process of Os-evolution.
This is the first book that provides the complete story of chloroplast biogenesis, from proplasti... more This is the first book that provides the complete story of chloroplast biogenesis, from proplastid to gerontoplast with mature chloroplast as the transient. Development of mature chloroplast from proplastid and subsequent transformation of the mature organelle to ...
Un modele mathematique est propose pour estimer la quantite de photons captes et l'efficacite... more Un modele mathematique est propose pour estimer la quantite de photons captes et l'efficacite photochimique du centre de reaction
The existing data do not suggest any mechanism of interaction between b-carotene in reaction cent... more The existing data do not suggest any mechanism of interaction between b-carotene in reaction centre (RC) and xanthophylls in light harvesting Chl-binding proteins (LHC) in photoprotecting chloroplasts. Out of two b -cars in RCII, one has been modeled after the position of b-carcis of bacterial reaction centre and the second b-car in D1 protein with all-trans form (b -cartrans). (1) The existence of a fast futile cycle around RCII with turnover time less than 50m s has tempted us to suggest that b-cartrans along with the accessory Chl a can initiate such a cycle and annul the effect of long lived P680+ during photoinhibition. (2) Formation of a molecular quenching complex consisting of zeaxanthin, Chl a and LHC is worked out. The possible excitonic coupling between b-carcis at RCII and the quenching complex is suggested. The excitation energy from 3b -carcis may be chanelled to the quenching complex at interface of RCII and LHCII. The b -carstrans present in core antenna (CP43, CP47)...
Journal of Biomolecular Structure and Dynamics, 2021
Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-Co... more Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compelled the scientific community to search for an effective drug that can cure or a vaccine that can prevent the disease. Alternatively, symptomatic treatment and traditional immunity boosters are prescribed. Holy Tulsi (Ocimum sanctum) has been known as an ancient remedy for cure of common cold and respiratory ailment. Several reports have come on virtual screening of phytochemicals including those of Tulsi against various enzymes of the virus. We undertook in silico analysis of the ethanol extracted phytochemicals of Tulsi as inhibitors of SARS-CoV-2 (2019-nCoV) main protease with an approach to look into the possibility of covalent ligand binding with the catalytic residue Cys145, which makes the report unique. The results suggest that the flavonoids and polyphenolic compounds of Tulsi, have potential to covalently bind to the catalytic residue Cys145 of main protease and irreversibly inhibit the viral enzyme. Luteolin-7-O-glucuronide is specially considered for its optimum properties, namely, low toxicity (LD50 5000 mg/kg body weight), high drug-likeness score (0.71), the active site binding free energy (ΔGbind) -19.19 kcal/mol by GBSA method and covalent binding energy -24.23 kcal/mol. Further experimental validations are required to establish the theoretical findings.Communicated by Ramaswamy H. Sarma.
Density Functional Theory (DFT) and Quantitative Structure-Activity Relationship (QSAR) studies w... more Density Functional Theory (DFT) and Quantitative Structure-Activity Relationship (QSAR) studies were performed on four benzimidazoles (compounds 1-4) and two benzothiazoles (compounds 5 and 6), previously synthesized by our group. The compounds were also investigated for their binding affinity and interactions with the SARS-CoV-2 Mpro (PDB ID: 6LU7) and the human angiotensin-converting enzyme 2 (ACE2) receptor (PDB ID: 6M18) using a molecular docking approach. Compounds 1, 2, and 3 were found to bind with equal affinity to both targets. Compound 1 showed the highest predictive docking scores, and was further subjected to molecular dynamics (MD) simulation to explain protein stability, ligand properties, and protein-ligand interactions. All compounds were assessed for their structural, physico-chemical, pharmacokinetic, and toxicological properties. Our results suggest that the investigated compounds are potential new drug leads to target SARS-CoV-2.
Epidermal growth factor receptor tyrosine kinase domain (EGFR-TKD) plays a pivotal role in cellul... more Epidermal growth factor receptor tyrosine kinase domain (EGFR-TKD) plays a pivotal role in cellular signaling, growth, and metabolism. The EGFR-TKD is highly expressed in cancer cells and was endorsed as a therapeutic target for cancer management to overcome metastasis, cell proliferation, and angiogenesis. The novel thiazolo-[2,3-b]quinazolinones series were strategically developed by microwave-assisted organic synthesis and multi dominos reactions aimed to identify the potent thiazolo-[2,3-b]quinazolinone inhibitor against EGFR-TKD. This study explores the binding stability and binding strength of newly developed series via molecular docking, molecular dynamics simulation, and MM/ PBSA and MM/GBSA calculations. The binding interaction was observed to be through the functional groups on aryl substituents at positions 3 and 5 of the thiazolo-[2, 3-b] quinazolinone scaffold. The methyl substituents at position 8 of the ligands had prominent hydrophobic interactions corroborating their bindings similar to the reference FDAapproved drug erlotinib in the active site. ADMET predictions reveal that derivatives 5ab, 5aq, and 5bq are drug-like and may be effective in in vitro study. Molecular dynamics simulation for 100 ns of docked complexes revealed their stability at the atomistic level. The ΔGbinding of thiazolo-[2,3-b]quinazolinone was found to be 5ab − 22.45, 5aq − 22.23, and 5bq − 20.76 similar to standard drug, and erlotinib − 24.11 kcal/mol was determined by MM/GBSA method. Furthermore, the anti-proliferative activity of leads of thiazolo-[2,3b]quinazolinones (n = 3) was studied against breast cancer cell line (MCF-7) and nonsmall lung carcinoma cell line (H-1299). The highest inhibitions in cell proliferation were shown by 5bq derivatives, and the IC 50 was found to be 6.5 ± 0.67 µM against MCF-7 and 14.8 µM against H-1299. The noscapine was also taken as a positive control and showed IC 50 at higher concentrations 37 ± 1 against MCF-7 and 46.5 ± 1.2 against H-1299.
Chloroplast development describes the life cycle of plastids from the proplastid to the mature ch... more Chloroplast development describes the life cycle of plastids from the proplastid to the mature chloroplast, which is subsequently transformed to a gerontoplast and finally to a necrotic plastid. Similar to any living system, the chloroplast may be defined as an open thermodynamic system far away from equilibrium. It has self-organized dissipative structures, namely, metabolome and genome, which fluctuate with development. The proplastid grows to become a mature chloroplast with self-organizing metabolic networks consisting of core, plastic, and signaling subsystems. The major function of the chloroplast is photosynthesis. Light induces redox reactions resulting finally into the synthesis of sugars. The photoelectron transport systems and sugars are not only two components of the core metabolic network, but these are also elements of signaling subsystems. The signaling regulatory and metabolic networks associated with chloroplast development are complex in nature and therefore are not fully understood. Many experimental data in the area remain to be explained without ambiguity. Examination of chloroplast development with respect to time, structure and fluctuations under the lens of non-equilibrium thermodynamics may contribute to our understanding of the process.
The transformations of proplastid to chloroplast and subsequently chloroplast to gerontoplast are... more The transformations of proplastid to chloroplast and subsequently chloroplast to gerontoplast are tightly coupled to the leaf development. The assembly and organization of chloroplast occur during leaf growth and expansion whereas the process of disassembly of the organelle starts when leaf turns yellow during senescence. Both assembly and disassembly processes are controlled by several factors with active participation of both plastid and nuclear genes. In both the cases the nuclear genome plays a major regulatory role although the role of a plastid factor in controlling some of the events has been suggested.
Zenodo (CERN European Organization for Nuclear Research), Mar 31, 1995
Schiff bases derived from 4,4'-diaminodiphenylsulphone with salicyladehyde and 2-hydroxy-1-naphth... more Schiff bases derived from 4,4'-diaminodiphenylsulphone with salicyladehyde and 2-hydroxy-1-naphthaldehyde behave as ON-x-NO donor doubl("bidentate ligands and form dinuclear complexes with divalent Co, Ni, Cu, Zn, Cd and Hg ions. The Co 1 , Ni 11 and Cuu complexes are found to be either octahedral or distorted-octahedral, whereas a tetradedral stereochemistry can be assigned to the Zn 11 , Cd 11 and Hg 11 complexes. The complexes have been characterised by analytical, conductance, magnetic, ir, electronic, esr and nmr spectral data.
Received 01 September 2014; accepted 10 September 2014 Abstract The kinks (bends) in helices play... more Received 01 September 2014; accepted 10 September 2014 Abstract The kinks (bends) in helices play an important role in functions of transmembrane proteins. Kinked helices are believed to be required for appropriate helix-helix and protein-protein interaction in membrane protein complexes. Therefore, knowledge of kink and its prediction from amino acid sequences is of great help in understanding the function of proteins. However, determination of kink in transmembrane α-helices is a computationally intensive task. In this paper we have developed Neural Network method based on radial basis function for prediction of kink in the helices with a prediction efficiency of 85%. A feature vector generated using three physico-chemical properties such as alpha propensity, coil propensity, and EIIP constituted in kinked helices contains most of the necessary information in determining the kink location. The proposed method captures this information more effectively than existing methods. Keywords Kink, Transmembrane α-helices, RBF, Feature vector, Physico-chemical properties. Knowledge of segments of transmembrane proteins and the bends in helices help in the study of tertiary structure and hence understanding the role played by that protein. 20-30% of all the proteins in any organism are membrane proteins. These are of particular importance because they form targets for over 60% of drugs on the market. Transmembrane α-helix bundle is a common structural feature of membrane proteins except porins, which contains β-barrels. Membrane spanning α-helices differ from their globular counterpart by the presence of helix breakers, Pro and Gly, in the middle of helices. Pro is known to induce a kink in the helix 1,2 . A hypothesis suggests that Pro is
Background: Harvesting solar energy through artificial photosynthetic device is gaining momentum ... more Background: Harvesting solar energy through artificial photosynthetic device is gaining momentum in the present era. Artificial photosynthetic device is a promising solution to the energy crisis by overcoming the crunch in fossil fuel and low efficiency of heat engine. Objective: An attempt has been made to design in silico an artificial photoreaction center mimicking the photosynthetic reaction center II. Method: A closely packed transmembrane four helix bundle protein with all the helices interacting with one another (PDB ID 2bl2) is selected for the purpose. The protein is suitably mutated in silico to accommodate the basic elements of a reaction center: oxidizing moiety, reducing moiety and photosensitizerto achieve the desired function of photo-redox reaction. Results: A model has been built. The transmembrane orientation in the artificial membrane system and energetic feasibility of photoredox reaction of the molecular device has been validated theoretically. Conclusion: A syn...
Objective: Lysin specific demethylase 1 (LSD1) inhibits the tumor suppressor activity of p53 and ... more Objective: Lysin specific demethylase 1 (LSD1) inhibits the tumor suppressor activity of p53 and facilitates the progress of tumor. In order to check the tumor growth, the activity of LSD1 enzyme is to be blunted.Methods: Phytochemicals from naturally occurring plant-based anti-cancer compound-activity-target (NPACT) database are screened with LSD1 as target applying genetic algorithm (GA) method to study best ligand poses and free energy of binding using Argus Lab. The prediction of drug-likeness and oral toxicity of the ligands are performed by the online tools Molsoft and ProTox respectively.Results: Calyxin H shows optimum binding affinity to both the substrate and FAD binding sites of LSD1. The LD50 value (median lethal dose) of calyxin H is more than 1000 mg/kg body weight and the toxicity class is 4.Conclusions: Calyxin H is the inhibitor of choice against target LSD1. The lead molecule may be the future potential herbal drug for cancer treatment.
The 33 kD extrinsic polypeptide binds to D1 and D2 polypeptides of reaction center II (RC II) of ... more The 33 kD extrinsic polypeptide binds to D1 and D2 polypeptides of reaction center II (RC II) of thylakoid from the lumen side (1–3). The pKa value of the polypeptide is reported to be 5.2 (4). The nature of binding of the 33 kD polypeptide to D1/D2 or membrane is not established. However, the polypeptide dissociates from its binding site by Ca2+, tris washing, heat treatment and high pH, but it does not dissociate by NaCl washing (5). Further, the polypeptide is reported to (i) regulate S3 → S0 transition of oxygen evolving system (6) (ii) maintain the conformation of oxygen evolving complex (7) (iii) stabilize Mn associated with oxygen evolution (5) (iv) accumulate Cl− required for oxygen evolution (5) and (v) have Mn—oxidase activity (8).
A model for the oxidation of water in chloroplasts is suggested. This model is based on certain p... more A model for the oxidation of water in chloroplasts is suggested. This model is based on certain physico-chemical principles and it accommodates the experimental results associated with the O,-evolving system. The model consists of two pools of heterogeneously bound manganese. Two manganese ions are bound to an enzyme system containing a water-splitting site and four manganese ions are bound to another protein system which connects the reaction centre of photosystem II to the water-splitting enzyme. The latter pool of manganese acts as an electron carrier and an electron trap. It is proposed that water is oxidised in the enzyme system to form H202 and 0; as transient species, and finally liberates 0,. This pathway is energetically feasible. The model explains the flash yield kinetics of O,-evolution and the action of various artificial electron donors and inhibitors of photosystem II. It gives a molecular picture and the quantum requirements of the redox reactions associated with the process of Os-evolution.
This is the first book that provides the complete story of chloroplast biogenesis, from proplasti... more This is the first book that provides the complete story of chloroplast biogenesis, from proplastid to gerontoplast with mature chloroplast as the transient. Development of mature chloroplast from proplastid and subsequent transformation of the mature organelle to ...
Un modele mathematique est propose pour estimer la quantite de photons captes et l'efficacite... more Un modele mathematique est propose pour estimer la quantite de photons captes et l'efficacite photochimique du centre de reaction
The existing data do not suggest any mechanism of interaction between b-carotene in reaction cent... more The existing data do not suggest any mechanism of interaction between b-carotene in reaction centre (RC) and xanthophylls in light harvesting Chl-binding proteins (LHC) in photoprotecting chloroplasts. Out of two b -cars in RCII, one has been modeled after the position of b-carcis of bacterial reaction centre and the second b-car in D1 protein with all-trans form (b -cartrans). (1) The existence of a fast futile cycle around RCII with turnover time less than 50m s has tempted us to suggest that b-cartrans along with the accessory Chl a can initiate such a cycle and annul the effect of long lived P680+ during photoinhibition. (2) Formation of a molecular quenching complex consisting of zeaxanthin, Chl a and LHC is worked out. The possible excitonic coupling between b-carcis at RCII and the quenching complex is suggested. The excitation energy from 3b -carcis may be chanelled to the quenching complex at interface of RCII and LHCII. The b -carstrans present in core antenna (CP43, CP47)...
Journal of Biomolecular Structure and Dynamics, 2021
Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-Co... more Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compelled the scientific community to search for an effective drug that can cure or a vaccine that can prevent the disease. Alternatively, symptomatic treatment and traditional immunity boosters are prescribed. Holy Tulsi (Ocimum sanctum) has been known as an ancient remedy for cure of common cold and respiratory ailment. Several reports have come on virtual screening of phytochemicals including those of Tulsi against various enzymes of the virus. We undertook in silico analysis of the ethanol extracted phytochemicals of Tulsi as inhibitors of SARS-CoV-2 (2019-nCoV) main protease with an approach to look into the possibility of covalent ligand binding with the catalytic residue Cys145, which makes the report unique. The results suggest that the flavonoids and polyphenolic compounds of Tulsi, have potential to covalently bind to the catalytic residue Cys145 of main protease and irreversibly inhibit the viral enzyme. Luteolin-7-O-glucuronide is specially considered for its optimum properties, namely, low toxicity (LD50 5000 mg/kg body weight), high drug-likeness score (0.71), the active site binding free energy (ΔGbind) -19.19 kcal/mol by GBSA method and covalent binding energy -24.23 kcal/mol. Further experimental validations are required to establish the theoretical findings.Communicated by Ramaswamy H. Sarma.
Density Functional Theory (DFT) and Quantitative Structure-Activity Relationship (QSAR) studies w... more Density Functional Theory (DFT) and Quantitative Structure-Activity Relationship (QSAR) studies were performed on four benzimidazoles (compounds 1-4) and two benzothiazoles (compounds 5 and 6), previously synthesized by our group. The compounds were also investigated for their binding affinity and interactions with the SARS-CoV-2 Mpro (PDB ID: 6LU7) and the human angiotensin-converting enzyme 2 (ACE2) receptor (PDB ID: 6M18) using a molecular docking approach. Compounds 1, 2, and 3 were found to bind with equal affinity to both targets. Compound 1 showed the highest predictive docking scores, and was further subjected to molecular dynamics (MD) simulation to explain protein stability, ligand properties, and protein-ligand interactions. All compounds were assessed for their structural, physico-chemical, pharmacokinetic, and toxicological properties. Our results suggest that the investigated compounds are potential new drug leads to target SARS-CoV-2.
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Papers by Mukesh Raval