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J Biomol Struct Dyn. 2019 Apr;37(7):1700-1714. doi: 10.1080/07391102.2018.1464958. Epub 2018 May 4.

In silico identification and screening of CYP24A1 inhibitors: 3D QSAR pharmacophore mapping and molecular dynamics analysis.

Author information

1
a Department of Bioinformatics , Alagappa University , Karaikudi , Tamilnadu , India.
2
b Department of Chemical Engineering , Konkuk University , 1 Hwayang-Dong, Gwangin-Gu, Seoul , South Korea.

Abstract

Vitamin D is a key signalling molecule that plays a vital role in the regulation of calcium phosphate homeostasis and bone remodelling. The circulating biologically active form of vitamin D is regulated by the catabolic mechanism of cytochrome P450 24-hydroxylase (CYP24A1) enzyme. The over-expression of CYP24A1 negatively regulates the vitamin D level, which is the causative agent of chronic kidney disease, osteoporosis and several types of cancers. In this study, we found three potential lead molecules adverse to CYP24A1 through structure-based, atom-based pharmacophore and e-pharmacophore-based screening methods. Analysis was done by bioinformatics methods and tools like binding affinity (binding free energy), chemical reactivity (DFT studies) and molecular dynamics simulation (protein-ligand stability). Combined computational investigation showed that the compounds NCI_95001, NCI_382818 and UNPD_141613 may have inhibitory effects against the CYP24A1 protein.

KEYWORDS:

screening; CYP24A1; DFT analysis; molecular dynamics; vitamin D

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