GdnHCl-induced unfolding intermediate in the mitochondrial carbonic anhydrase VA

Idrees, Danish; Prakash, Amresh; Haque, Md. Anzarul; Islam, Asimul; Hassan, Md. Imtaiyaz; Ahmad, Faizan

doi:10.1016/j.ijbiomac.2016.06.080

Cited by 15 publications

(1 citation statement)

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“…Intramolecular H-bonding is one of the fundamental aspects of structural stability in protein (Idrees et al, 2016(Idrees et al, , 2017a(Idrees et al, , 2017b. The intramolecular H-bonding formed within 3.5 Å was calculated to explore the rearrangement of interactions in CAII during the simulation.…”

Section: Dynamics Of Interactions In the Caii Complexes: Hydrogen Bond Analysismentioning

confidence: 99%

Discovery of Natural Compounds as Potential Inhibitors of Human Carbonic Anhydrase II: An Integrated Virtual Screening, Docking, and Molecular Dynamics Simulation Study

Anjum

Ali

Shafie

et al. 2021

OMICS: A Journal of Integrative Biology

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Carbonic anhydrase II (CAII) is one of the zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide, leading to the formation of bicarbonate and proton. CAII plays a significant role in health and disease. For example, CAII helps to maintain eye pressure while regulating the pH of the tumor microenvironment, and by extension, contributing to cancer progression. Owing to its remarkable role in cancer, visual health, and other human diseases, CAII can serve as an attractive therapeutic target. We report an original study based on high-throughput virtual screening of natural compounds from the ZINC database in search of potential inhibitors of CAII. We selected the hits based on the physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, pan-assay interference compound (PAINS) patterns, and interaction analysis. Importantly, two natural compounds were identified, ZINC08918123 and ZINC00952700, bearing considerable affinity and specific interactions to the residues of the CAII-binding pocket with well-organized conformational fitting compatibility. We investigated the conformational dynamics of CAII in complex with the identified compounds through molecular dynamics simulation, which revealed the formation of a stable complex preserved throughout the 100 ns trajectories. The stability of the protein/ligand complexes is maintained by significant numbers of noncovalent interactions throughout the simulations. In conclusion, natural compounds identified in the present study specifically and computerassisted drug design broadly offer a reliable resource and strategy to discover potential promising therapeutic inhibitors of CAII to cure various cancers and glaucoma after further experimental validation and clinical studies.

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Section: Dynamics Of Interactions In the Caii Complexes: Hydrogen Bond Analysismentioning

confidence: 99%