Sequential docking

Sequential docking, where pre-enumerated compounds are docked into the receptor binding site, scored, ranked, and selected for further experimental testing the conformational... 

An alternative to sequential docking can be followed if combinatorial libraries are evaluated. Quite a few programs have been specifically designed for speed-up by so-called combinatorial docking. They profit from the structured, incremental nature of combinatorial libraries and the fact that molecules of a combinatorial library consist of a common core. This core is assumed to form common specific interactions with the receptor (possibly supported by experimental evidence) and can thus be prepositioned in the binding pocket in one or a few similar orientations. It then serves as skeleton for the addition of substituents. Obviously, this step is ideally suited for incremental construction algorithms (361)... 

A sequential process should always be set up to focus the compound set, as much as possible, for time-consuming investigations like flexible docking. 

The mechanism depicted in Fig. 13.9d is only a schematic of the basic mechanochemical cycle. Fundamental chemical transitions such as ATP hydrolysis and ADP release are not depicted because our data do not uniquely locate these transitions. In a simple sequential model, in which each subunit binds ATP, hydrolyzes it, releases products, and steps, before activating the next subunit, these processes are uniquely determined by the simple requirement that ATP is hydrolyzed before products are released. However, in a more complicated kinetic model in which the individual hydrolysis cycles of the identical subunits are interwoven, such as that depicted in Fig. 13.9, there is no longer a single unique position for these important kinetic events. ATP hydrolysis, for example, might occur immediately after the tight binding of each ATP and before the next subunits is active for ATP docking. 

Sollner T, Bennett MK, Whiteheart SW, Scheller RH, Rothman JE (1993) A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell 75 409 18. 

SollnerTH, Bennett MK, Whiteheart SW, Scheller RH, Rothman JE (1993 b) A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. In Cell 75 409-18 Stecher B, Weller U, Habermann E, Gratzl M, Anhert-Hilger G (1989) The light chain but not the heavy chain of botulinum A toxin inhibits exocytosis from per-meabilized adrenal chromaffin cells. In FEBS Lett. 255 391 -4... 

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