Docking schemes

In any docking scheme, two conflicting requirements must be balanced (i) the desire for a robust and accurate procedure and (ii) reasonable run time of the laboratory workstation for the computational method chosen. 

PTPIB, Protein tyrosine phosphatase-IB. The table is provided to allow comparison of docking schemes with respect to the algorithms and target proteins. 

The object of the refinement procedure is to move from a completely rigid-body docking scheme to include both flexibility of the side-chains together with a limited re-orientation of the two interacting molecules. Thus the refinement procedure is an iterative two step approach repeated until convergence involving ... 

Strategy was to implement a flexible docking scheme because it was felt that both molecules of the complex may change their conformations during association. 

Fig. 12.23 Two simple scoring functions used in docking. On the left is the basic scoring scheme used by the DOCK program [Desjarlais et al. 1988], On the right is the piecewise linear potential [Cclhaar et al. 1995],...

Scheme 9.9 Biohydroxylation utilizing the docking/protecting group concept.

Figure 14-11. Snapshots from the conformational switch path explored in the vicinity of the active conformation (unfolded docked conformation) and starting from the inactive (undocked) conformation found in crystal. Stems A and B were aligned (best fitted) and are shown in yellow, different instances of stem C are shown in stick representation with different colors. A schematic of the non-canonical binding scheme of the ligation site is shown in the right panel and the general mechanism of ligation in the left panel...

Subtypes of Rab, particularly Rab3, have been implicated in the regulation of exocytosis and neurotransmitter release at nerve terminals (see also Chs 9 and 10) [30,31]. One possible scheme by which this might occur is shown in Figure 19-5. In its GTP-bound form, Rab associates with synaptic vesicles and interacts with other membrane proteins to create a complex unfavorable for vesicle docking and perhaps fusion. Upon depolarization of the nerve terminal, a Rab GAP is activated, which results in dissociation of the GDP form of Rab from the vesicle membrane. This enables the synaptic vesicle to proceed with... 

Recently, the synthesis of (5)-2-hydroxy-2-methylbutyric acid has been reported using the docking/protecting group concept and HNL from Hevea brasiliensis (ffl>HNL) as catalyst (Scheme 8.1). ... 

Scheme 8.1 Chemoenzymatic synthesis of (S)-2-hydroxy-2-methylhutyric acid by using the docking protecting group concept...

As shown by Turner et fluorescence experiments using a 5 -pyrenylated oligonucleotides have aided the determination of rate constants and equilibrium constants that define (a) the initial base-pairing step in substrate binding, (b) the so-called docking step that reflects a substrate-induced conformational step, and (c) the bond cleavage step per se. The scheme shown in Fig. 3 represents a beautiful example of Koshland s induced-fit model at work in ribozyme action. 

Tertiary alcohols are very unreactive toward hydrolases. There are, however, exceptions. Some enzymes have a certain amino acid motif located in the oxyanion binding pocket that allows the docking of space-demanding alcohols such as tertiary ones into the acylated enzyme [104]. One such hydrolase is Candida antarctica lipase A (CALA), which has been found to catalyze the acylation of the tertiary 2-phenyl-3-butyn-2-ol rac-110 by vinyl acetate in organic solvents. Thus efficient resolution of 110 was achieved in isooctane at room temperature (Scheme 4.34) [105]. 

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