Predicted structures of new Vitamin D Receptor agonists based on available X-ray structures

- Electrostatic forces are important factors in molecular recognition e.g. receptor-agonist.
- New rational design of vitamin D analogs is proposed using electrostatic interaction energy as a scoring function.
- Designed agonists have all advantages of previously synthesized and crystallized agonists.

Current efforts in the field of vitamin D are to develop 1,25(OH)2D3 analogs that exhibit equal or even increased anti-proliferative activity while possessing a reduced tendency to cause hypercalcemia. The study proposes a new, rational design of vitamin D analogs based on data available in the Protein Data Bank. Undertaken approach was to minimize the electrostatic interaction energies available after the reconstruction of charge density with the aid of the pseudoatom databank, namely the University at Buffalo Pseudoatom Databank (UBDB). Analysis of 24 vitamin D analogs, bearing similar molecular structures complexed with Vitamin D Receptor enabled the design of new agonists forming all advantageous interaction to the receptor, coded TB1, TB2, TB3 and TB4.