Identification of natural marine compounds as potential inhibitors of CDK2 using molecular docking and molecular dynamics simulation approach

Ahmad, Basharat; Saeed, Aamir; Castrosanto, Melvin A.; Zia, Muhammad Amir; Farooq, Umar; Abbas, Zaheer; Khan, Sara

doi:10.1080/07391102.2022.2135594

Cited by 8 publications

(1 citation statement)

References 37 publications

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“…Likewise, the site finder tool of MOE [ 53 ] was utilized to investigate the key player binding residues of HDACs with Zn 2+ and generate electrostatic surface maps that include these residues to identify docking active sites. The drug-like library of compounds along with co-crystalized ligand apicidin were subjected to molecular docking into the specified docking sites of HDACs enzymes [ 54 ]. We applied triangular algorithms to identify the ten different docking poses of each molecule.…”

Section: Methodsmentioning

confidence: 99%

Investigating Potential Cancer Therapeutics: Insight into Histone Deacetylases (HDACs) Inhibitions

Ahmad,

Saeed,

Al-Amery

et al. 2024

Pharmaceuticals

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Histone deacetylases (HDACs) are enzymes that remove acetyl groups from ɛ-amino of histone, and their involvement in the development and progression of cancer disorders makes them an interesting therapeutic target. This study seeks to discover new inhibitors that selectively inhibit HDAC enzymes which are linked to deadly disorders like T-cell lymphoma, childhood neuroblastoma, and colon cancer. MOE was used to dock libraries of ZINC database molecules within the catalytic active pocket of target HDACs. The top three hits were submitted to MD simulations ranked on binding affinities and well-occupied interaction mechanisms determined from molecular docking studies. Inside the catalytic active site of HDACs, the two stable inhibitors LIG1 and LIG2 affect the protein flexibility, as evidenced by RMSD, RMSF, Rg, and PCA. MD simulations of HDACs complexes revealed an alteration from extended to bent motional changes within loop regions. The structural deviation following superimposition shows flexibility via a visual inspection of movable loops at different timeframes. According to PCA, the activity of HDACs inhibitors induces structural dynamics that might potentially be utilized to define the nature of protein inhibition. The findings suggest that this study offers solid proof to investigate LIG1 and LIG2 as potential HDAC inhibitors.

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Section: Methodsmentioning

confidence: 99%