Computational analysis of PTP-1B site-directed mutations and their structural binding to potential inhibitors

Tasleem, Munazzah; Shoaib, Ambreen; AL-Shammary, Asma Ayyed; Abdelgadir, Abdelmushin; Alsamar, Zeina; Jamal, Qazi Mohammad Sajid; Alrehaily, Abdulwahed; Bardcki, Fevzi; Sulieman, Abdel Moneim Elhadi; Upadhyay, Tarun Kumar; Ansari, Irfan Ahmad; Lai, Dakun; Badraoui, Riadh; Yadav, Dharmendra Kumar

doi:10.14715/cmb/2022.68.7.13

Cited by 6 publications

(4 citation statements)

References 24 publications

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“…Drug-protein binding interaction is significant parameter to better understand the molecular docking results and to deeply understand the conformational behavior 210 , 211 . Top six drug having docking energy greater than − 7.00 kcal/mol were selected to check the binding conformation behavior and draggability behavior of MADD.…”

Section: Resultsmentioning

confidence: 99%

Computational prognostic evaluation of Alzheimer’s drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches

Hassan,

Shahzadi,

Yasir

et al. 2023

Sci Rep

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Drug designing is high-priced and time taking process with low success rate. To overcome this obligation, computational drug repositioning technique is being promptly used to predict the possible therapeutic effects of FDA approved drugs against multiple diseases. In this computational study, protein modeling, shape-based screening, molecular docking, pharmacogenomics, and molecular dynamic simulation approaches have been utilized to retrieve the FDA approved drugs against AD. The predicted MADD protein structure was designed by homology modeling and characterized through different computational resources. Donepezil and galantamine were implanted as standard drugs and drugs were screened out based on structural similarities. Furthermore, these drugs were evaluated and based on binding energy (Kcal/mol) profiles against MADD through PyRx tool. Moreover, pharmacogenomics analysis showed good possible associations with AD mediated genes and confirmed through detail literature survey. The best 6 drug (darifenacin, astemizole, tubocurarine, elacridar, sertindole and tariquidar) further docked and analyzed their interaction behavior through hydrogen binding. Finally, MD simulation study were carried out on these drugs and evaluated their stability behavior by generating root mean square deviation and fluctuations (RMSD/F), radius of gyration (Rg) and soluble accessible surface area (SASA) graphs. Taken together, darifenacin, astemizole, tubocurarine, elacridar, sertindole and tariquidar displayed good lead like profile as compared with standard and can be used as possible therapeutic agent in the treatment of AD after in-vitro and in-vivo assessment.

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Section: Resultsmentioning

confidence: 99%

Computational prognostic evaluation of Alzheimer’s drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches

Hassan,

Shahzadi,

Yasir

et al. 2023

Sci Rep

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“…Accumulation of data from numerous studies has demonstrated the contribution of various missense SNPs to the progression of diverse diseases 36 , 37 , 40 . However, there is a paucity of knowledge regarding the alterations in OX1R structural and conformational dynamics caused by detrimental missense SNPs.…”

Section: Discussionmentioning

confidence: 99%

“…Single nucleotide polymorphisms (SNPs) represent a prevalent and stable type of genetic variation within the human genome. They not only serve as valuable biological markers but can also be linked to the development of complex diseases, abnormalities, and variations in drug responses 36 – 40 . Nonsynonymous SNPs (nsSNPs) in protein-coding regions, which result in alterations to amino acid sequences and the potential creation of mutated proteins with new structural and functional properties, have garnered significant interest.…”

Section: Introductionmentioning

confidence: 99%

Unraveling the function and structure impact of deleterious missense SNPs in the human OX1R receptor by computational analysis

Farajzadeh-Dehkordi,

Mafakher,

Harifi

et al. 2024

Sci Rep

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The orexin/hypocretin receptor type 1 (OX1R) plays a crucial role in regulating various physiological functions, especially feeding behavior, addiction, and reward. Genetic variations in the OX1R have been associated with several neurological disorders. In this study, we utilized a combination of sequence and structure-based computational tools to identify the most deleterious missense single nucleotide polymorphisms (SNPs) in the OX1R gene. Our findings revealed four highly conserved and structurally destabilizing missense SNPs, namely R144C, I148N, S172W, and A297D, located in the GTP-binding domain. Molecular dynamics simulations analysis demonstrated that all four most detrimental mutant proteins altered the overall structural flexibility and dynamics of OX1R protein, resulting in significant changes in the structural organization and motion of the protein. These findings provide valuable insights into the impact of missense SNPs on OX1R function loss and their potential contribution to the development of neurological disorders, thereby guiding future research in this field.

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“…Besides, 4,5-dicafeoyl quinic acid and 3,5-dicafeoyl quinic acid are also recognized for their ability to inhibit DPPIV and glucosidase, respectively [87]. Some work also reported that 1,5 dicafeoylquinic acid had a dosedependent protective efect against glucotoxicity in RIN-m5F cells [88][89][90]. In 2007, Ren et al [91] administered chlorogenic acid to rats and observed rapid absorption and a relatively slow distribution followed by a slower elimination phase.…”

Section: Chlorogenic Acidmentioning

confidence: 99%

Antidiabetic Potential of Phytochemicals Found in Vernonia amygdalina

Talwar,

Chakraborty,

Zahera

et al. 2024

Journal of Chemistry

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Type 2 diabetes mellitus (T2DM), or “insulin-independent diabetes mellitus,” is a worldwide health concern. Diabetes affects roughly 415 million individuals worldwide, with 193 million undiagnosed cases. The number of people afflicted in the following decades is predicted to double. Although various synthetic medications are currently available to treat/manage T2DM, their side effects compel researchers to seek novel treatment options. Because of their affinity for biological receptors and broad bioactivity, nature has long been a source of innovative medication. V. amygdalina is one of the numerous natural productswith antidiabetic properties. Several studies have shown that the extracts have antidiabetic effects in vitro and in vivo. This review examined the antidiabetic and pharmacokinetic characteristics of phytoconstituents found in V. amygdalina.

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Computational analysis of PTP-1B site-directed mutations and their structural binding to potential inhibitors

Cited by 6 publications

References 24 publications

Computational prognostic evaluation of Alzheimer’s drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches

Computational prognostic evaluation of Alzheimer’s drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches

Unraveling the function and structure impact of deleterious missense SNPs in the human OX1R receptor by computational analysis

Antidiabetic Potential of Phytochemicals Found in Vernonia amygdalina

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