Protein structures docking techniques

Protein-based methods rely upon the structural information extracted from the X-ray crystallographic and/or homology protein structures. These also include docking techniques for the exploration of possible binding modes of a ligand to a given transporter protein. 

In reaction with the active heme complex, compound 1, it is often assumed that the first stage is homolytic hydrogen abstraction, resulting in radical formation. This is certainly likely to occur with aliphatic hydroxylation. Ideally a calculation of the transition state should be carried out, but this is difficult in practice. Relative radical stabilities have therefore been used as an approximation. In a typical calculation one generates all possible radicals for a substrate, optimizes them, and determines their relative stabilities. They are then docked into the 3D protein structure using constraints between the heme and the sites predicted from the radical calculations. Early descriptions of this approach made use of homology models, but the same techniques can obviously be used with crystal structures. 

Connolly developed a computational technique for docking two protein structures based on matching complementary patterns of knobs and holes (106). The algorithm was used to predict the association of the a and fi subunits of hemoglobin to form the corrext a-/ dimer. 

The most common docking technique that attempts to account for protein flexibility uses multiple protein stmctures. The ensemble of structures is expected to represent the range of conformations sampled by the protein and has the benefit of being able to evaluate both small and large conformational changes. The molecular docking is repeated for each individual protein conformation, which... 

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