Residues of a11 and a12 and the loop between them showed higher flexibility. The T877A-AR Acemetacin mutation located in a11 allows for a more spacious hormone-binding pocket and will accommodate steroids with different extensions within the D ring. The examination of the nature and size of the solvent accessible surface area of proteins is an important tool to measure potential interaction propensity with neighboring proteins. We calculated the average SASA of each AR complex from the 15 ns MD trajectory. No large differences were observed among the calculated SASAs of different AR mutant complexes. These results show that the differences are mostly associated with the a11 Ca12 regions of the AR-LBD, where the T877A mutation is located. Therefore, we decided to compare the dynamics among the eight different complexes, specifically in this region, by using RMSD matrices. The matrices, which essentially capture extreme movements, reveal regions of high flexibility, especially for CPA and dexamethasone, compared to other AR-ligand complexes. Computational modeling has also been carried out for a number of other AR somatic mutations in the ligand-binding domain, and show sensitivity to a broad range of hormone ligands, including, AR-W741L, -L701H, H874Y and -F876L. Determination of the LBD structure between AR-WT and -H874Y, when bound to Testosterone in the presence of the N-terminal FXXLF motif peptide or the TIF2 coactivator peptide, found that all structures Ascomycin conformed to the canonical nuclear receptor LBD fold. Moreover, the -H874Y DHT and R1881 structures conformed to T877A and W741L LBD bound to steroid and nosteroid ligands. The double AR-mutant cell lines MDAPCa-2a and MDA-PCa-2b, possess the L701H and T877A somatic mutations, these cells shows similar AR transactivation and LBD structural properties to the single AR-T877A mutant LNCaP cells to a broad spectrum of steroid ligands and antiandrogens, but also show an increased sensitivity cortisol steroids. Most recently, the structure AR-F876L mutations has been investigated that allows the cell to use the new anti-androgen enzalutamide as an agonist.