Theoretical study of molecular mechanism of binding TRAP220 coactivator to Retinoid X Receptor alpha, activated by 9-cis retinoic acid

Study on molecular mechanism of conformational reorientation of RXR-alpha ligand binding domain is presented. We employed CABS-a reduced model of protein dynamics to model folding pathways of binding 9-cis retinoic acid to apo-RXR molecule and TRAP220 peptide fragment to the holo form. Based on obtained results we also propose a sequential model of RXR activation by 9-cis retinoic acid and TRAP220 coactivator. Methodology presented here may be used for investigation of binding pathways of other NR/hormone/cofactor sets.