Structure-based design of promising natural products to inhibit thymidylate kinase from Monkeypox virus and validation using free energy calculations

Khan, Abbas; Adil, Shoaib; Qudsia, Hafiza Ayesha; Waheed, Yasir; Alshabrmi, Fahad M.; Wei, Dong‐Qing

doi:10.1016/j.compbiomed.2023.106797

Cited by 23 publications

(15 citation statements)

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“…This method determines BFE and binding stability of interacting key residues and is less expensive than most of chemical‐free energy methods. Moreover, its accuracy is recognized to be more than any rational scoring function 43–45 . This method can highlight the structure, function, and interaction that the mutations have on AccB binding to acetyl‐CoA, so we used MM/GBSA approach to calculate the BFE of each complex.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, its accuracy is recognized to be more than any rational scoring function. [43][44][45] This method can highlight TA B L E 3 Binding-free energy (BFE) results for the wild-type and mutant complexes. the structure, function, and interaction that the mutations have on AccB binding to acetyl-CoA, so we used MM/GBSA approach to calculate the BFE of each complex.…”

Section: Estimation Of the Binding-free Energy For The Wild-type And ...mentioning

confidence: 99%

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Improving the substrate binding of acetyl‐CoA carboxylase (AccB) from Streptomyces antibioticus through computational enzyme engineering

Ali,

Wei,

Khan

et al. 2024

Biotech and App Biochem

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Malonyl‐CoA serves as the main building block for the biosynthesis of many important polyketides, as well as fatty acid–derived compounds, such as biofuel. Escherichia coli, Corynebacterium gultamicum, and Saccharomyces cerevisiae have recently been engineered for the biosynthesis of such compounds. However, the developed processes and strains often have insufficient productivity. In the current study, we used enzyme‐engineering approach to improve the binding of acetyl‐CoA with ACC. We generated different mutations, and the impact was calculated, which reported that three mutations, that is, S343A, T347W, and S350W, significantly improve the substrate binding. Molecular docking investigation revealed an altered binding network compared to the wild type. In mutants, additional interactions stabilize the binding of the inner tail of acetyl‐CoA. Using molecular simulation, the stability, compactness, hydrogen bonding, and protein motions were estimated, revealing different dynamic properties owned by the mutants only but not by the wild type. The findings were further validated by using the binding‐free energy (BFE) method, which revealed these mutations as favorable substitutions. The total BFE was reported to be −52.66 ± 0.11 kcal/mol for the wild type, −55.87 ± 0.16 kcal/mol for the S343A mutant, −60.52 ± 0.25 kcal/mol for T347W mutant, and −59.64 ± 0.25 kcal/mol for the S350W mutant. This shows that the binding of the substrate is increased due to the induced mutations and strongly corroborates with the docking results. In sum, this study provides information regarding the essential hotspot residues for the substrate binding and can be used for application in industrial processes.

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Section: Resultsmentioning

confidence: 99%

Section: Estimation Of the Binding-free Energy For The Wild-type And ...mentioning

confidence: 99%

Improving the substrate binding of acetyl‐CoA carboxylase (AccB) from Streptomyces antibioticus through computational enzyme engineering

Ali,

Wei,

Khan

et al. 2024

Biotech and App Biochem

Self Cite

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“…This study identified 11 possible compounds for inhibition of thymidylate kinase, after screening hundreds of thousands of compounds (Sib Tul Hassan Shah and Naeem, 2023). Several small molecule inhibitors have also been studied shortlisting drugs like imatinib, conivaptan, lumacaftor, betulinic acid, and fluspirilene (Dutt et al, 2023;Khan et al, 2023).…”

Section: New Discoveriesmentioning

confidence: 99%

Re-emergence of neglected tropical diseases amid the COVID-19 pandemic: Epidemiology, transmission, mitigation strategies, and recent advances in chemotherapy and vaccines

K. Mohapatra,

Seidel,

Kandi

et al. 2023

Frontiers Research Topics

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Frontiers is more than just an open access publisher of scholarly articles: it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge. Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers journal seriesThe Frontiers journal series is a multi-tier and interdisciplinary set of openaccess, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing. All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community. At the same time, the Frontiers journal series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to qualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews. Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view. By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation. What are Frontiers Research Topics?Frontiers Research Topics are very popular trademarks of the Frontiers journals series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area.

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“…Currently, a number of different drugs have been shown to be effective against the Mpox when tested in vitro , such as Adamantane derivatives, Resveratol, Tecovirimat, Mitoxantrone, and Ribavirin. Nevertheless, their usefulness and safety in the context of Mpox have not been shown, and further basic and clinical research is needed ( Ali et al., 2023 ; Khan et al., 2023 ; Khani et al., 2023 ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to novel drugs, chemical ligands, broad-spectrum antivirals, and broadly neutralizing antibodies, it is worth noting that the prophylactic and therapeutic aspects of medicinal plants and herbs, their extracts and metabolites, phytochemicals, immunity-enhancing foods, and dietary nutrition have shown potentials for countering several important infectious pathogens and deadly viruses, including Mpox and MARV ( Khan et al., 2023 ; Nguyen, 2023 ; Pourhajibagher and Bahador, 2023 ). O-rhamnosides, including Kaempferol-O-rhamnosides, are a class of polyphenolic compounds with a variety of beneficial biological effects, such as antimicrobial, antioxidant, and anti-inflammatory properties ( León-Figueroa et al., 2022 ; Velavan and Meyer, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Mechanistic inhibition of Monkeypox and Marburg virus infection by O-rhamnosides and Kaempferol-o-rhamnosides derivatives: a new-fangled computational approach

Mashud

Kumer

Mukerjee

et al. 2023

Front. Cell. Infect. Microbiol.

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The increasing incidence of Monkeypox virus (Mpox) and Marburg virus (MARV) infections worldwide presents a significant challenge to global health, as limited treatment options are currently available. This study investigates the potential of several O-rhamnosides and Kaempferol-O-rhamnosides as Mpox and MARV inhibitors using molecular modeling methods, including ADMET, molecular docking, and molecular dynamics/MD simulation. The effectiveness of these compounds against the viruses was assessed using the Prediction of Activity Spectra for Substances (PASS) prediction. The study’s primary focus is molecular docking prediction, which demonstrated that ligands (L07, L08, and L09) bind to Mpox (PDB ID: 4QWO) and MARV (PDB ID: 4OR8) with binding affinities ranging from -8.00 kcal/mol to -9.5 kcal/mol. HOMO-LUMO based quantum calculations were employed to determine the HOMO-LUMO gap of frontier molecular orbitals (FMOs) and to estimate chemical potential, electronegativity, hardness, and softness. Drug similarity and ADMET prediction assessments of pharmacokinetic properties revealed that the compounds were likely non-carcinogenic, non-hepatotoxic, and rapidly soluble. Molecular dynamic (MD) modeling was used to identify the most favorable docked complexes involving bioactive chemicals. MD simulations indicate that varying types of kaempferol-O-rhamnoside are necessary for successful docking validation and maintaining the stability of the docked complex. These findings could facilitate the discovery of novel therapeutic agents for treating illnesses caused by the Mpox and MARV viruses.

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Structure-based design of promising natural products to inhibit thymidylate kinase from Monkeypox virus and validation using free energy calculations

Cited by 23 publications

References 56 publications

Improving the substrate binding of acetyl‐CoA carboxylase (AccB) from Streptomyces antibioticus through computational enzyme engineering

Improving the substrate binding of acetyl‐CoA carboxylase (AccB) from Streptomyces antibioticus through computational enzyme engineering

Re-emergence of neglected tropical diseases amid the COVID-19 pandemic: Epidemiology, transmission, mitigation strategies, and recent advances in chemotherapy and vaccines

Mechanistic inhibition of Monkeypox and Marburg virus infection by O-rhamnosides and Kaempferol-o-rhamnosides derivatives: a new-fangled computational approach

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