Lead generation docking

Abagyan R. Totrov M. High-throughpnt docking for lead generation. Curr Opin Chem Biol 2001 5 375-82. 

Abagyan, R., Totrov, M. High-throughput docking for lead generation. Curr. Opin. Chem. Biol. 2001, 5(4), 375-382. 

One element of database generation that is a key consideration is whether to expand the representative compounds to include alternative tautomers, protonated and deprotonated forms of the molecule, and also to enumerate stereochemistry fully if not specified in the input. Depending on the molecules in question and the options considered, these can lead to a 10-fold increase in the size of the database to be explored. However, such an expansion is necessary if methods are used that are sensitive to such chemical precision (e.g., docking). For 3D similarity searching, it is sometimes more efficient to consider various modifications to the query, leading to multiple searches against a smaller database. 

Neuromuscular transmission involves the events leading from the liberation of acetylcholine (ACh) at the motor nerve terminal to the generation of end plate currents (EPCs) at the postjunctional site. Release of ACh is initiated by membrane depolarization and influx of Ca++ at the nerve terminal (Fig. 28.1). This leads to a complex process involving docking and fusion of synaptic vesicles with active sites at the presynaptic membrane. Because ACh is released by exocytosis, functional transmitter release takes place in a quantal fashion. Each quantum corresponds to the contents of one synaptic vesicle (about 10,000 ACh molecules), and about 200 quanta are released with each nerve action potential. 

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