In silico identification and screening of CYP24A1 inhibitors: 3D QSAR pharmacophore mapping and molecular dynamics analysis.
John Marshal JayarajKrishnasamy GopinathJung-Kul LeeKarthikeyan MuthusamyPublished in: Journal of biomolecular structure & dynamics (2018)
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.
Keyphrases
- molecular dynamics
- molecular docking
- density functional theory
- molecular dynamics simulations
- chronic kidney disease
- binding protein
- bone mineral density
- postmenopausal women
- end stage renal disease
- high resolution
- risk assessment
- emergency department
- protein protein
- dna binding
- amino acid
- climate change
- peritoneal dialysis
- transcription factor
- electronic health record
- bioinformatics analysis
- drug induced