Methods
Successful docking requires two criteria:
- Generating a set configurations which reliably includes at least one nearly correct one.
- Reliably distinguishing nearly correct configurations from the others.
For many interactions, the binding site is known on one or more of the proteins to be docked. This is the case for antibodies and for competitive inhibitors. In other cases, a binding site may be strongly suggested by mutagenic or phylogenetic evidence. Configurations where the proteins interpenetrate severely may also be ruled out a priori.
After making exclusions based on prior knowledge or stereochemical clash, the remaining space of possible complexed structures must be sampled exhaustively, evenly and with a sufficient coverage to guarantee a near hit. Each configuration must be scored with a measure that is capable of ranking a nearly correct structure above at least 100,000 alternatives. This is a computationally intensive task, and a variety of strategies have been developed.
Read more about this topic: Macromolecular Docking
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