Natural defense against multi-drug resistant Pseudomonas aeruginosa: Cassia occidentalis L. in vitro and in silico antibacterial activity

Imon, Raihan Rahman; Kabir Talukder, Md. Enamul; Akhter, Shahina; Islam, Md. Saidul; Ahammad, Foysal; Anis-Ul-Haque, K. M.; Moniruzzaman, Md.; Afroze, Mirola; Khan, Mala; Hena Mostofa Jamal, Mohammad Abu; Wani, Tanveer A.; Uddin, Mohammad Jashim; Rahman, Md. Mashiar

doi:10.1039/d3ra03923d

Cited by 5 publications

(4 citation statements)

References 44 publications

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“…The color scheme is as follows: native (blue), I123S mutant (red), V456M mutant (green), D463G mutant (violet), R602H mutant (yellow), and R633W mutant (orange). A 50 ns molecular dynamics (MD) simulation was performed using the "Desmond v6.3 Program" in Schrodinger 2020-3 under the Linux framework 49 . The simulation was performed following the three-site transferrable intermolecular potential (TIP3P) water model 50 .…”

Section: Resultsmentioning

confidence: 99%

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In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene

Kamal,

Mia,

Faruque

et al. 2024

Sci Rep

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Single nucleotide polymorphisms (SNPs) are one of the most common determinants and potential biomarkers of human disease pathogenesis. SNPs could alter amino acid residues, leading to the loss of structural and functional integrity of the encoded protein. In humans, members of the minichromosome maintenance (MCM) family play a vital role in cell proliferation and have a significant impact on tumorigenesis. Among the MCM members, the molecular mechanism of how missense SNPs of minichromosome maintenance complex component 6 (MCM6) contribute to DNA replication and tumor pathogenesis is underexplored and needs to be elucidated. Hence, a series of sequence and structure-based computational tools were utilized to determine how mutations affect the corresponding MCM6 protein. From the dbSNP database, among 15,009 SNPs in the MCM6 gene, 642 missense SNPs (4.28%), 291 synonymous SNPs (1.94%), and 12,500 intron SNPs (83.28%) were observed. Out of the 642 missense SNPs, 33 were found to be deleterious during the SIFT analysis. Among these, 11 missense SNPs (I123S, R207C, R222C, L449F, V456M, D463G, H556Y, R602H, R633W, R658C, and P815T) were found as deleterious, probably damaging, affective and disease-associated. Then, I123S, R207C, R222C, V456M, D463G, R602H, R633W, and R658C missense SNPs were found to be highly harmful. Six missense SNPs (I123S, R207C, V456M, D463G, R602H, and R633W) had the potential to destabilize the corresponding protein as predicted by DynaMut2. Interestingly, five high-risk mutations (I123S, V456M, D463G, R602H, and R633W) were distributed in two domains (PF00493 and PF14551). During molecular dynamics simulations analysis, consistent fluctuation in RMSD and RMSF values, high Rg and hydrogen bonds in mutant proteins compared to wild-type revealed that these mutations might alter the protein structure and stability of the corresponding protein. Hence, the results from the analyses guide the exploration of the mechanism by which these missense SNPs of the MCM6 gene alter the structural integrity and functional properties of the protein, which could guide the identification of ways to minimize the harmful effects of these mutations in humans.

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Section: Resultsmentioning

confidence: 99%

“…To evaluate the structural stability of the mutant protein, a 50 ns molecular dynamics (MD) simulation was performed using the "Desmond v6.3 Program" in Schrodinger 2020-3 under the Linux framework 49 . The simulation was performed following the three-site transferrable intermolecular potential (TIP3P) water model 50 .…”

Section: Methodsmentioning

confidence: 99%

In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene

Kamal,

Mia,

Faruque

et al. 2024

Sci Rep

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“…The measurement of the surface area is essential in comprehending the dynamic nature of ligand–protein binding. It additionally provides information regarding the optimization of a site, the identification of the binding site, and the accessibility of ligands in macromolecular environments ( Imon et al, 2023 ). In this study, SASA, MolSA, and PSA of the surface area were carried out over the course of a 150 ns simulation of proteins in complex with the four lead compounds, namely, CID 95842900 (red), CID 137030374 (orange), CID 124958150 (gray), and CID 110126793 (yellow).…”

Section: Resultsmentioning

confidence: 99%

Cheminformatics-based identification of phosphorylated RET tyrosine kinase inhibitors for human cancer

Talukder,

Aktaruzzaman,

Siddiquee

et al. 2024

Front. Chem.

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BackgroundRearranged during transfection (RET), an oncogenic protein, is associated with various cancers, including non-small-cell lung cancer (NSCLC), papillary thyroid cancer (PTC), pancreatic cancer, medullary thyroid cancer (MTC), breast cancer, and colorectal cancer. Dysregulation of RET contributes to cancer development, highlighting the importance of identifying lead compounds targeting this protein due to its pivotal role in cancer progression. Therefore, this study aims to discover effective lead compounds targeting RET across different cancer types and evaluate their potential to inhibit cancer progression.MethodsThis study used a range of computational techniques, including Phase database creation, high-throughput virtual screening (HTVS), molecular docking, molecular mechanics with generalized Born surface area (MM-GBSA) solvation, assessment of pharmacokinetic (PK) properties, and molecular dynamics (MD) simulations, to identify potential lead compounds targeting RET.ResultsInitially, a high-throughput virtual screening of the ZINC database identified 2,550 compounds from a pool of 170,269. Subsequent molecular docking studies revealed 10 compounds with promising negative binding scores ranging from −8.458 to −7.791 kcal/mol. MM-GBSA analysis further confirmed the potential of four compounds to exhibit negative binding scores. MD simulations demonstrated the stability of CID 95842900, CID 137030374, CID 124958150, and CID 110126793 with the target receptors.ConclusionThese findings suggest that these selected four compounds have the potential to inhibit phosphorylated RET (pRET) tyrosine kinase activity and may represent promising candidates for the treatment of various cancers.

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“…To evaluate the structural stability of the protein, a 50 ns MD simulation was performed using the “Desmond v6.3 Program” in Schrodinger 2020-3 under the Linux framework [ 28 ]. The simulation was examined by the three-site transferrable intermolecular potential (TIP3P) water model [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Prediction and assessment of deleterious and disease causing nonsynonymous single nucleotide polymorphisms (nsSNPs) in human FOXP4 gene: An in-silico study

Kamal,

Teeya,

Rahman

et al. 2024

Heliyon

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Natural defense against multi-drug resistant Pseudomonas aeruginosa: Cassia occidentalis L. in vitro and in silico antibacterial activity

Abstract: Cassia occidentalis L. is widely used in indigenous and traditional medicine, but its impact on multi-drug resistant (MDR) bacterial infections mostly remains unknown.

Cited by 5 publications

References 44 publications

In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene

In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene

Cheminformatics-based identification of phosphorylated RET tyrosine kinase inhibitors for human cancer

Prediction and assessment of deleterious and disease causing nonsynonymous single nucleotide polymorphisms (nsSNPs) in human FOXP4 gene: An in-silico study

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