Mapping the binding region

In order to characterise the three-dimensional design constraints imposed by the receptor, a first class of methods attempts to locate target sites within the binding cavity that will yield the crucial favourable interactions with predefined probes. The probes can be individual atoms - site points - or small fragments e.g. functional groups like carbonyl or methyl, water, which search for hot spots in the active site, as it is illustrated in figure 1. Examples of these methods are GRID [32, 33], MCSS [34], HSITE [35] and LUDl [36]. 

GRID and MCSS use classical mechanics potential functions for scoring and selecting the fragments, and are usually called energy based methods [37]. 

Whether the fragment placement is direct or via site point connection, the methods have the obvious advantage of rapidly locating the hot spots in the 

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