Targets rational drug design

The lead discovery process is depicted in Figure 10.4-4 and shows how the different methods are interconnected. A lead structure can be discovered by serendipity. In rational drug design all information available about a target serves to direct... 

Dyason JC, Wilson JC, Von Itzstein M. Sialidases Targets for rational drug design. In Bultinck P, De Winter H, Langenaeker W, Tollenaere JP, editors. Computational medicinal chemistry for drug discovery. New York Dekker, 2004. 

Huntington JA, Baglin TP. Targeting thrombin -rational drug design from natural mechanisms. Trends Pharmacol Sci 2003 24 589-95. 

Rational drug design - use of high resolution molecular imaging techniques (NMR, x-ray crystallography) to identify the active site of the target molecule and construct an new active substance which binds to this active site. 

Where the structure has not been determined or cannot be determined experimentally by diffraction techniques or spectroscopy, then molecular mechanics can be used as a predictive tool. This is of particular value when the structure of a compound is the main target, such as in modeling associated with rational drug design (see Chapter 12). 

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