Exploring the effect of temperature on inhibition of non-structural protease 3 of Chikungunya virus using molecular dynamics simulations and thermodynamics parameters

Kumar, Durgesh; Meena, M. K.; Kumari, Kamlesh; Kumar, Rajesh; Bahadur, Indra; Jain, Pallavi; Singh, Prashant

doi:10.1016/j.molliq.2021.116164

Cited by 9 publications

(12 citation statements)

References 51 publications

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“…85 However, this value has been considered acceptable according to Kumar et al (2021). 84 The – LQM467 RMSD presented a similar stability profile as the free NS2B/NS3 pro (Fig. 4A), except that no increase was observed at the first 35–40 ns.…”

Section: Resultsmentioning

confidence: 66%

“…Regarding the native protein, low RMSD values for the protein–ligand complex of less than 1.5 Ångström (Å) or even better less than 1 Å are acceptable, representing a trustworthy binding mode of a ligand into a cavity (or binding site) from a native protein. 84 Since all acrylamide inhibitors exhibited a competitive binding mode as observed by our experimental approaches, their results towards will be discussed in detail. However, all results for Ramachandran plots for all protease–ligand complexes can be found in Fig.…”

Section: Resultsmentioning

confidence: 84%

“…Molecular dynamics (MD) simulations can be utilized to study the time-dependent interaction and behavior of small molecules with the target. 84 In this context, this in silico approach has been frequently used in studies involving structural aspects and active compounds toward NS2B/NS3 pro . 85–90 Considering that LQM467 , 471 , 472 , and 474 are competitive inhibitors, we decided to investigate their interactions with the catalytic site of DENV-2 NS2B/NS3 pro in the closed conformation (PDB: ).…”

Section: Resultsmentioning

confidence: 99%

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Fragment-based design of α-cyanoacrylates and α-cyanoacrylamides targeting Dengue and Zika NS2B/NS3 proteases

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Section: Resultsmentioning

confidence: 66%

Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 99%

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Fragment-based design of α-cyanoacrylates and α-cyanoacrylamides targeting Dengue and Zika NS2B/NS3 proteases

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“…The radius of gyration is the square root of the inertia moment of atoms (Equation (3)), where n is the number of atoms, r i depicts the atomic position and r m represents the mean position of all atoms. Herein, we evaluated the RoG of peramivir wildtype and E119V mutant complexes, as depicted in Figure 4 , using CPPTRAJ within the AMBER 18 suite [ 48 ].

…”

Section: Resultsmentioning

confidence: 99%

Intermolecular Mechanism and Dynamic Investigation of Avian Influenza H7N9 Virus’ Susceptibility to E119V-Substituted Peramivir–Neuraminidase Complex

et al. 2022

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The H7N9 virus attaches itself to the human cell receptor protein containing the polysaccharide that terminates with sialic acid. The mutation of neuraminidase at residue E119 has been explored experimentally. However, there is no adequate information on the substitution with E119V in peramivir at the intermolecular level. Therefore, a good knowledge of the interatomic interactions is a prerequisite in understanding its transmission mode and subsequent effective inhibitions of the sialic acid receptor cleavage by neuraminidase. Herein, we investigated the mechanism and dynamism on the susceptibility of the E119V mutation on the peramivir–neuraminidase complex relative to the wildtype complex at the intermolecular level. This study aims to investigate the impact of the 119V substitution on the neuraminidase–peramivir complex and unveil the residues responsible for the complex conformations. We employed molecular dynamic (MD) simulations and extensive post-MD analyses in the study. These extensive computational investigations were carried out on the wildtype and the E119V mutant complex of the protein for holistic insights in unveiling the effects of this mutation on the binding affinity and the conformational terrain of peramivir–neuraminidase E119V mutation. The calculated total binding energy (ΔGbind) for the peramivir wildtype is −49.09 ± 0.13 kcal/mol, while the E119V mutant is −58.55 ± 0.15 kcal/mol. The increase in binding energy (9.46 kcal/mol) is consistent with other post-MD analyses results, confirming that E119V substitution confers a higher degree of stability on the protein complex. This study promises to proffer contributory insight and additional knowledge that would enhance future drug designs and help in the fight targeted at controlling the avian influenza H7N9 virus. Therefore, we suggest that experimentalists collaborate with computational chemists for all investigations of this topic, as we have done in our previous studies.

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“…2DR binds with the histidine amino acid with the oxygen of the carboxyl group and glutamine. As reported, molecular docking provides an idea but not a very reliable tool; therefore, one has to perform MD simulations of the complex of the Mpro of nCoV with the ligand used in molecular docking at 300 K to attain a better understanding of the stability and solubility of the complex formed [67][68][69].…”

Section: Molecular Dockingmentioning

confidence: 99%

In Silico Evaluation of Binding of 2-Deoxy-D-Glucose with Mpro of nCoV to Combat COVID-19

et al. 2022

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COVID-19 has threatened the existence of humanity andthis infection occurs due to SARS-CoV-2 or novel coronavirus, was first reported in Wuhan, China. Therefore, there is a need to find a promising drug to cure the people suffering from the infection. The second wave of this viral infection was shaking the world in the first half of 2021. Drugs Controllers of India has allowed the emergency use of 2-deoxy-D-glucose (2DG) in 2021 for patients suffering from this viral infection. The potentiality of 2-deoxy-D-glucose to intervene in D-glucose metabolism exists and energy deprivation is an effective parameter to inhibit cancer cell development. Once 2DG arrives in the cells, it becomes phosphorylated to 2-deoxy-D-glucose-6-phosphate (2-DG6P), a charged molecule expressively captured inside the cells. On the other hand, 2DG lacks the ability to convert into fructose-6-phosphate, resulting in a hampering of the activity of both glucose-6-phosphate isomerase and hexokinase, and finally causing cell death. Hence, the potential and effectiveness of 2DG with the main protease (Mpro) of novel coronavirus (nCoV) should be investigated using the molecular docking and molecular dynamics (MD) simulations. The ability of 2DG to inhibit the Mpro of nCoV is compared with 2-deoxyglucose (2DAG), an acyclic molecule, and 2-deoxy-D-ribose (2DR). The binding energy of the molecules with the Mpro of nCoV is calculated using molecular docking and superimposed analysis data is obtained. The binding energy of 2DG, 2DR and 2DAG was −2.40, −2.22 and −2.88 kcal/mol respectively. Although the molecular docking does not provide reliable information, therefore, the binding affinity can be confirmed by molecular dynamics simulations. Various trajectories such as Rg, RMSD, RMSF, and hydrogen bonds are obtained from the molecular dynamics (MD) simulations. 2DG was found to be a better inhibitor than the 2DAG and 2DR based on the results obtained from the MD simulations at 300 K. Furthermore, temperature-dependent MD simulations of the Mpro of nCoV with promising 2DG was performed at 295, 310 and 315 K, and the effective binding with the Mpro of nCoV occurred at 295 K. With the use of DFT calculations, optimized geometry and localization of electron density of the frontier molecular orbitals were calculated.

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Exploring the effect of temperature on inhibition of non-structural protease 3 of Chikungunya virus using molecular dynamics simulations and thermodynamics parameters

Cited by 9 publications

References 51 publications

Fragment-based design of α-cyanoacrylates and α-cyanoacrylamides targeting Dengue and Zika NS2B/NS3 proteases

Fragment-based design of α-cyanoacrylates and α-cyanoacrylamides targeting Dengue and Zika NS2B/NS3 proteases

Intermolecular Mechanism and Dynamic Investigation of Avian Influenza H7N9 Virus’ Susceptibility to E119V-Substituted Peramivir–Neuraminidase Complex

In Silico Evaluation of Binding of 2-Deoxy-D-Glucose with Mpro of nCoV to Combat COVID-19

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