Factor modeled inhibitor complexes

Rao MS, Olson AJ. Modelling of factor Xa-inhibitor complexes A computational flexible docking approach. Prot Struct Fund Gen 1999 34 173-83. 

Bcl-2 is one of the many factors that control apoptosis, and overexpression of Bcl-2 has been observed in many different cancers. A homology model of Bcl-2 was derived from the NMR 3D structure of the Bcl-XL complex with a Bak BH3 peptide. This model served to search the NCI 3D database of 206,876 organic compounds for potential Bcl-2 inhibitors, which bind to the Bak BH3 binding site of Bcl-2. Full conformational flexibility of the ligands was taken into account in the program DOCK. Thirty-five potential inhibitors were tested, and seven of them had IC50 values from 1.6 to W.OpM. One of... 

While the x-ray structure of native Factor Xa has been reported [4] the nature of its crystal packing, specifically the fact that the active site of one Factor Xa molecule is blocked by the N-terminus of a second resulting in a continuous polymeric structure, apparently has precluded diffusing inhibitors into the preformed crystals to obtain complexes. Complexes with inhibitors cocrystallized with Factor Xa also have not been reported [81]. Thus, efforts to do structure-based design with this enzyme have relied on molecular modeling. 

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