Protein binding pocket

This indicates how favorable it is to take the ligand out of solution and into the protein binding pocket. 

Morris RRJ, Najmanovich RRJ, Kahraman A et al (2005) Real spherical harmonic expansion coefficients as 3D shape descriptors for protein binding pocket and ligand comparisons. Bioinformatics (Oxford, England) 21 2347-2355... 

Brady GP, Stouten PE (2000) Fast prediction and visualization of protein binding pockets with PASS. J Comput Aided Mol Des 14 383-401... 

Distance between the ligand (geometrical center) and the center of specific protein binding pockets (e.g., where in the protein does the ligand bind ) ... 

As it is not yet possible to prepare tailored protein binding pockets from their constituent amino acids, existing, well-characterized protein structures represent attractive starting materials for the design of new enzymes. These can be used as scaffolding on which to mount catalytic groups. For instance, Kaiser and co-workers have... 

A noteworthy chemometrical method (CHEMDOCK) for establishing complementary relationships between receptors and ligands has been devised by Oloff et al. [122], Their approach employs atomic descriptors derived by quantum chemical methods (TAE/RECON descriptors [123]), which represent both the ligand structures and the protein binding pockets in global a descriptor space. 

Through systematic modification of the imidazole-appended 2-phenyl-aminobenzoate peptidomimetic scaffold (e.g., FTI-2148) a group at Abbott Pharmaceuticals have identified an expanded series of inhibitors that lack either the C-terminal Met carboxylate (as in compounds 14-23 of Ref. [55]) or the imidazole group (as in ABT-839) [56,70,71]. This latter compound became a clinical candidate and demonstrates that coordination to the zinc ion is not a prerequisite for potent inhibitors of FT. In place of metal-ligand (imidazole, thiol, etc.) coordination, ABT-839 exploits hydrophobic contact from the cyclohexylethyl and -butyl groups to the protein-binding pocket. For the structures of other CaaX peptidomimetics, please refer to Table 6.1. 

Figure 6 Mechanisms of translesion synthesis, (a) Activation mechanism of Pol V during translesion synthesis. Pol V is a heterotrimer composed of subunits UmuC, D 2 UmuC is the catalytic domain, and UmuD is the product of RecA mediated proteolysis. Translesion synthesis by Pol V is activated by the presence of a RecA filament in trans. (b) Model of DNA polymerase switching during translesion synthesis. Pol III and Pol IV each bind to a p protomer at a conserved hydrophobic protein binding pocket (QL[S/D]LF). 1. Pol III is arrested at the site of DNA damage, whereas Pol IV is held in an inactive state away from the DNA. 2. Pol IV gains hold of the primer terminus from Pol III at the stall site Pol III is now held away from the DNA. 3. Pol IV extends the DNA past the lesion. 4. Pol III regains hold of the primer terminus from Pol IV.

FIGURE 21.11 Trifluoperazine, a ligand of Ca -calmodulin that induce an adaptation of the protein binding pocket. 

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