دلسازي به روش هومولوژي و شبيه سازي ديناميك مولكولي پروتيين Rab23 انساني به هدف انجام مطالعات Docking با ليگاند كلسترول

Homology Modeling and Molecular DynamicSimulation of Human Rab23 in associationwith Docking Study of Cholesterol Ligand

Rab23 يكي از پروتيينهاي خانواده Rab مي باشد كه مسوول تنظيم ادغام و اتصال غشا ويزيكولها با اندامكهاي سلولهاي يوكاريوتي مي باشد. اين پروتيين يك تنظيم كننده منفي خودكار سلولي براي علامت دهي(Signaling) hedgehog در مهره داران است. مسير علامت دهي hedgehog در رشد اكثر ارگانها و بافتهاي مهره داران نقش محوري داشته و ارتباط آن با نقايص مادرزادي و بسياري از انواع تومورها مشخص شده است. بنابراين دخالت Rab23 در اين مسير و ناهنجاريهاي بياني آن در بسياري از انواع بيماريها ديده مي شود. از جمله بيماريهايي كه ناشي از جهش در ژن اين پروتيين و يا به طور كلي بيان غير نرمال آن مي باشند عبارتند از: سندرمهاي Carpenter و Gorlin، كارسينوماي تيروييد، هپاتوسل كارسينوما، تومورزايي و انواع مختلف سرطان.

Background and aim: Rab23 is a member of the Rab family of proteins that regulate the fusion and docking of vesicle membranes to membrane of eukaryotic cells. This protein is a spontaneous negative regulator of hedgehog signaling in vertebrates. Hedgehog signaling has a critical role in tissue and organs of vertebrates which has associate with congenital disorders and many types of tumors. Therefore, inclusion of Rab23 is suggested in this pathway and expression anomalies. Mutation of the gene of Rab23 and abnormal expression of this protein can cause some diseases such as: Gorlin and Carpenter syndrome, thyroid carcinoma, hepatocell carcinoma, tumors and different types of cancers. Matherial and methods: Modelling of this protein was done via Modeller9V7 by selection a suitable template with high similarity fom PDB database. The best model was selected by Procheck for simulation step and then molecular dynamic simulation was done via GROMACS. Autodock4.2 was used for docking analysis of Rab23 with cholesterol for determination of binding sites. Results: Stability of RMSD and energy plot showed that the constructed 3D model is stable and close to reality. Docking analysis displayed some binding sites for cholesterol. Conclusion: Having binding site for cholesterol suggests that this protein performes its role in docking to vesicle memberane through the region possesed cholesterol in association with other proteins such as GLI2 and GLI3. Owing to biological importance of Rab23, simulation of this protein in silico could be beneficial for therapeutic purposes in drug design and/or inhibitory ligands. Ling, molecular dynamic simulation