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The aim of this study is to compare affinity of ligand to bind with receptors Based on molecular dynamic modulation.
In this study common VDR polymorphism in Iranian population detected. RFLP-PCR was used in large samples and followed by sequencing several segment of LBD in specific samples. These data used as main material for simulation of LBD nano- structure.
We used various modules of several software packages to carry out the modeling calculation, first superposing all of the known NR-LBD structures to define the positions of helices and the shape of the ligand pocket with bound ligand.
This simulation of VDR- LBD associate with result of IMOS Study about functional analysis of interaction between vitamin D and VDR provides a modulation of vitamin D signaling and agonistic conformation for comparing analogs efficiency .
Genotypes of the vitamin D receptor classified in seven major groups that only in three genotypic groups were associated with the serum concentrations of calcium or other biochemical values, calciotropic hormones, or markers of bone turnover.
These groups selected as main genotype of VDR to simulate variation of LBD. Molecular modeling indicated that these variations could be cause decrease of ligand affinity to bind. The location of the side chain hydroxyl group is critical for binding 1, 25(OH)2D3 to VDR and other binding proteins through hydrogen bonding, hydrophobic and van der Waals interactions. Natural ligand had lower affinity form general estimations and before studies. This decrease in fitness could corrected by add two new bounds in natural ligand.
Finding of this study confirm by other investigation that show the side chain of the hormone is to interact with the AF-2 region in helix 12 of the VDR-LBD .
This interaction helps stabilize the transcriptionally active conformation of the VDR .Suggesting analog for best result need to functional assays. Vitamin D analog designing based on VDR structure may improve some unexplained problem such as high prevalence of any cancers and autoimmune diseases.
This study is an example of application of nano technology in medicine especially in endocrinology. We suggest molecular modeling as away to investigate effect of receptor genetic variations on LBD-ligand interaction.
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