STUDIES ON THE STRUCTURE-ACTIVITY RELATIONSHIP OF RETINOIDSMOLECULAR MODELING OF INTERACTION BETWEEN SELECTIVE RETINOIDS AND NUCLEAR RECEPTORS

AIM: All these efforts provide the basis for designing new and selective retinoid drugs. METHODS AND RESULTS: The sequence alignment based upon RARγ(retinoic acid nuclear receptors γ) crystal structural motifs was performed, and showed that only three amino acid residues of RARα, RARβ, RARγ in the ligand-binding pocket are at variance. These divergent residues are obvious features to account for the RAR selectivity of certain retinoid. Meanwhile, the ligand binding domains of holo-RAR(α,β) were modeled by “site mutagenesis technique”. Molecular dynamics relaxing and global minimization were carried out and led to construction of the final complex models. The interaction of RAR(α,β,γ) and their specific ligand by docking simulation were investigated, the fine binding patterns have been used to define clearly some important structural characteristics of selective retinoids. CONCLUSION: Receptor-specific retinoids possess improved activity/toxicity profiles compared with the non-selective counterparts. Molecular design based on the known structure of receptor presents a hopeful prospect.