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E-Pharmacophore mapping and docking studies on Vitamin D receptor (VDR)
Selvaraman Nagamani1, Chandrasekhar Kesavan, Karthikeyan Muthusamy
1Department of Bioinformatics, Alagappa University, Karaikudi 630 004, India.
Bioinformation
|October 12, 2012
Summary
Researchers identified potential new drug compounds to treat vitamin D receptor (VDR) deficiencies, which cause metabolic disorders in chronic kidney disease patients. This computational study used molecular docking and pharmacophore modeling to find these promising VDR agonists.
Area of Science:
- Molecular Medicine
- Computational Chemistry
- Pharmacology
Background:
- Small molecules are crucial in molecular medicine due to predictable properties and target binding.
- Reduced vitamin D receptor (VDR) expression is linked to calcium-phosphate metabolic disorders in Chronic Kidney Disease (CKD).
Purpose of the Study:
- To identify novel chemical compounds that can enhance vitamin D receptor (VDR) synthesis.
- To find potential therapeutic agents for calcium-phosphate metabolic disorders associated with CKD.
Main Methods:
- Utilized computer-aided drug design, including molecular docking and pharmacophore filtering.
- Developed an energy-optimized pharmacophore model based on known VDR agonists.
- Screened large compound libraries (Asinex, TOSLab, Binding, Zinc) against the VDR pharmacophore model.
- Applied Glide docking (HTVS, SP, XP) for virtual screening and hit identification.
Main Results:
- A pharmacophore model was generated with specific features: one hydrogen bond acceptor (A), one hydrogen bond donor (D), and two hydrophobic regions (H).
- Virtual screening identified five potential lead compounds (BD_230, BD_12938, BD_18601, BD_19517, BD_19584) with high fitness scores.
- These compounds showed promise as VDR agonists for treating metabolic disorders.
Conclusions:
- The study successfully identified potential lead molecules for VDR-related metabolic disorders using computational methods.
- The developed VDR pharmacophore model serves as a valuable tool for future drug discovery efforts.
- These identified compounds warrant further investigation for therapeutic potential in CKD patients.
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