Abreu, Rui M.V.

Ferreira, Isabel C.F.R.

Froufe, Hugo J.C.

Biblioteca Digital do IPB

Farnesoid X Receptor: Docking Model Validation Hugo Froufe', RuiM. V. Abreu'·", Isabel C.F.R. Ferreira' 'CIMO-ESAB, lns t. Politécnico de Bragança, Campus deSta Apolónia, 5301-855 Bragança, Portugal ] 'Centro de Genética e Biotecnologia-IBB, Univ. Trás-os-Montes e Alto Douro, 5001-801 Vila Real, Portugal Farnesoid X receptor (FXR) is a protein that was shown to be in-volved in controlling numerous metabolic pathways that include: maintaining bile acid, lipid and glucose homeostasis, preventing in-testinal bacterial infection and modulating liver regeneration and tumorigenesis [1]. TI1e different roles played by FXR highlight poten-tial new opportunities for using FXR as a drug target for different diseases [2]. ln this worl< we validate the use of FXR as a target for virtual docking simulation experiments. We used the docking softw·are Autodock 4 as it is acknowledged to be one of the most widely used in docking simulations [3]. The FXR 3 -D structure used (PDB code: 10SH) in this study is co-crystaJlized with Fexaramine, a known high affinity agonist. Before the docking experiment, Fexaramine was removed from the structure. A docking experiment was then performed using Fexaramine as ligand and the docking results showed that the predicted binding mode essentially matches the Fexaramine present in the experimental FXR 3-D struc-ture, with a RMSD (Root Mean Standard Deviation) of less than 1 À on average, a cluster of 49 in 50 runs and a minimum binding energy of -14.39 kcal/mol. We also evaluate the FXR against other known agonists. These results valida te the use of the FXR 3D structure as a good target for virtual docking experiments with other potential ligands. [1] Y. Zhang, and P.A. Edw3rds, FEBS Lett. 582 (2oo8) 1o-8. I ]2] Y.D. W3ng, W.D. Chen, D.D. Moore, and W. Huang, Cell Res. {2oo8), doi : 1o.J0)8/ cr.2oo8.289. I [3) G.M. Morris, D.S. Goodsell , R.S. Halliday, R. Huey, W.E. Hart, R.K. Belew, and A.J. O!son, Journal ofCom putational Chemistry. 19 (1998) 1639-1662. 84 

Farnesoid X receptor: docking model validation

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Farnesoid X receptor: docking model validation

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