Structural and quantum mechanical computations to elucidate the altered binding mechanism of metal and drug with pyrazinamidase from Mycobacterium tuberculosis due to mutagenicity

Rasool, Nouman; Iftikhar, Saima; Amir, Anam; Hussain, Waqar

doi:10.1016/j.jmgm.2017.12.011

Cited by 18 publications

(6 citation statements)

References 23 publications

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“…In literature, no study has been reported previously targeting the analysis of compound reactivity within the binding pocket of TMV proteins. However, DFT based analysis is reported in some other studies and the band energy gaps of the present study are also within the same range as those reported in previous studies [25][26][27]. The lower band energy gap reflects higher reactivity of compounds as the ELUMO and EHOMO are responsible for the charges transferred in a chemical reaction [28].…”

Section: Discussionsupporting

confidence: 89%

Penta-1,4-Diene-3-One Oxime Derivatives Strongly Inhibit the Replicase Domain of Tobacco Mosaic Virus: Elucidation Through Molecular Docking and Density Functional Theory Mechanistic Computations

Hussain¹,

Ali²,

Afzalv³

et al. 2018

J Antivir Antiretrovir

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Tobacco mosaic virus (TMV) is one of the major concerns to the farmers as it infects several crops of economic importance such as tomato. The mechanism of viral infection in host initiates on the entry of TMV in the host cell and production of a capping enzyme i.e. RNA polymerase. Replication of virus produces multiple mRNAs which further encodes multiple proteins including coat proteins, movement proteins and an RNA-dependent RNA polymerase (RdRp). In the present study, TMV replicase domain has been targeted using a set of novel penta-1,4-diene-3-one oxime derivatives bearing a pyridine moiety. To further assess the reactivity of these compounds against TMV, molecular orbital energy descriptors were calculated using Density Functional Theory (DFT) correlations. The pharmacokinetics and pharmacological properties have also been analysed as the crop yields are to be consumed by the humans. Results revealed that among the 16 derivatives of penta-1,4-diene-3-one oxime, compound C, J, O and P showed the highest inhibitory potential. Reactivity of these compounds was also high, however, only compound C showed effective pharmacokinetics and pharmacological properties. Based on these results, it is concluded that compound C can be used as a potent inhibitor against TMV and the yields produced by a crop will be safe to be consumed by humans.

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Section: Discussionsupporting

confidence: 89%

Penta-1,4-Diene-3-One Oxime Derivatives Strongly Inhibit the Replicase Domain of Tobacco Mosaic Virus: Elucidation Through Molecular Docking and Density Functional Theory Mechanistic Computations

Hussain¹,

Ali²,

Afzalv³

et al. 2018

J Antivir Antiretrovir

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“…These energies can characterize the electrophilic or nucleophilic nature of a compound. Therefore, the screened phytochemicals illustrated the higher reactivity of these phytochemicals, as reported in various previous studies [ 23 – 25 , 27 , 30 – 33 , 35 , 52 , 65 ].…”

Section: Resultssupporting

confidence: 79%

“…E x GGA is the generalized gradient approximation for the Becke 88 functional while the E c GGA reflects the correlation functional of Lee-Yang-Parr. With this hybrid functional, local density approximation is added in the form of E c LDA [ 52 ].…”

Section: Methodsmentioning

confidence: 99%

Phytochemicals from Selective Plants Have Promising Potential against SARS‐CoV‐2: Investigation and Corroboration through Molecular Docking, MD Simulations, and Quantum Computations

Kousar¹,

Majeed

Yasmin

et al. 2020

BioMed Research International

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Coronaviruses have been reported previously due to their association with the severe acute respiratory syndrome (SARS). After SARS, these viruses were known to be causing Middle East respiratory syndrome (MERS) and caused 35% evanescence amid victims pursuing remedial care. Nowadays, beta coronaviruses, members of Coronaviridae, family order Nidovirales, have become subjects of great importance due to their latest pandemic originating from Wuhan, China. The virus named as human-SARS-like coronavirus-2 contains four structural as well as sixteen nonstructural proteins encoded by single-stranded ribonucleic acid of positive polarity. As there is no vaccine available to treat the infection caused by these viruses, there is a dire need for taking necessary steps against this virus. Herein, we have targeted two nonstructural proteins of SARS-CoV-2, namely, methyltransferase (nsp16) and helicase (nsp13), respectively, due to their substantial activity in viral pathogenesis. A total of 2035 compounds were analyzed for their pharmacokinetics and pharmacological properties. The screened 108 compounds were docked against both targeted proteins and were compared with previously reported known compounds. Compounds with high binding affinity were analyzed for their reactivity through DFT analysis, and binding was analyzed using molecular dynamics simulations. Through the analyses performed in this study, it is concluded that EryvarinM, Silydianin, Osajin, and Raddeanine can be considered potential inhibitors for MTase, while TomentodiplaconeB, Osajin, Sesquiterpene Glycoside, Rhamnetin, and Silydianin for helicase after these compounds are validated thoroughly using in vitro and in vivo protocols.

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“…is the local density approximation. To analyse the reactivity of phytochemicals in the binding pocket of MTase and RdRp, band energy gaps were calculated using the expression ELUMO-EHOMO 19,20 . Phytochemicals along with the interacting residues from binding pocket were considered for the calculations and for each phytochemical, the conformer with maximum binding energy was analysed.…”

Section: Dft Study Of Phytochemicals and Band Energy Gap Analysismentioning

confidence: 99%

Probing the Pharmacological Parameters, Molecular Docking and Quantum Computations of Plant Derived Compounds Exhibiting Strong Inhibitory Potential Against NS5 from Zika Virus

Rasool

Jalal²,

Amjad

et al. 2018

Braz. arch. biol. technol.

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Zika virus (ZIKV) is known for microcephaly and neurological disease in humans and the nonstructural proteins of ZIKV play a fundamental role in the viral replication. Among the seven nonstructural proteins, NS5 is the most conserved and largest protein. Two major functional domains of NS5 i.e. methyltransferase (MTase) and RNAdependent RNA polymerase (RdRp) are imperative for the virus life cycle and survival. The present study explicates the inhibitory action of phytochemicals from medicinal plants against NS5 from ZIKV, leading to the identification of potential inhibitors. The crystal structure of the protein is retrieved from RCSB protein data bank. A total of 2035 phytochemicals from 505 various medicinal plants are analysed for their pharmacological properties and pharmacokinetics. Compounds having effective drug-likeness are docked against the protein and further analysed using density functional theory approach. Among the 2035 phytochemicals, 13 are selected as potential inhibitors against MTase having high binding affinities and 17 compounds are selected for RdRp. HOMO and LUMO energies are calculated for the docked compounds within and outside binding pockets of MTase and RdRp, adapting the B3LYP hybrid exchange-correlation functional with def2-SV(P) basis set. Physicochemical properties such as ionization energy, electronic chemical potential, electronegativity, electron affinity, molecular softness, molecular hardness and electrophilicity index have also been analysed for selected phytochemicals. Based upon the results, it is concluded that the selected phytochemicals are highly competent to impede the replication of the virus by inhibiting the ZIKV-NS5.

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Structural and quantum mechanical computations to elucidate the altered binding mechanism of metal and drug with pyrazinamidase from Mycobacterium tuberculosis due to mutagenicity

Cited by 18 publications

References 23 publications

Penta-1,4-Diene-3-One Oxime Derivatives Strongly Inhibit the Replicase Domain of Tobacco Mosaic Virus: Elucidation Through Molecular Docking and Density Functional Theory Mechanistic Computations

Penta-1,4-Diene-3-One Oxime Derivatives Strongly Inhibit the Replicase Domain of Tobacco Mosaic Virus: Elucidation Through Molecular Docking and Density Functional Theory Mechanistic Computations

Phytochemicals from Selective Plants Have Promising Potential against SARS‐CoV‐2: Investigation and Corroboration through Molecular Docking, MD Simulations, and Quantum Computations

Probing the Pharmacological Parameters, Molecular Docking and Quantum Computations of Plant Derived Compounds Exhibiting Strong Inhibitory Potential Against NS5 from Zika Virus

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