Structure-based drug design discovery

There are three main contributions that structural methods are making to the drug discovery process—structural biology, structure-based design, and structure-based discovery. 

In this chapter we have given an overview of the two major approaches used in NMR and drug discovery, structure-based design and NMR-based screening. Both areas are flourishing and, together with more traditional uses of NMR, they demonstrate the versatility of NMR as a tool in medicinal chemistry. The power of NMR has been dramatically enhanced over the last decade by developments... 

Keywords Alzheimer s disease- Aspartic acid protease- BACE-1- Fragment-based drug discovery- Structure-based design... 

K. (2002) PROSELECT combining structure-based drug design and array-based chemistry for rapid lead discovery. 2. The development of a series of highly potent and selective factor Xa inhibitors. Journal of Medicinal Chemistry, 45, 1221-1232. 

Kubinyi H1998. Structure-based Design of Enzyme Inhibitors and Receptor Ligands. Current Opinion i. Drug Discovery and Development 1 5-15. 

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Also in the 1980s, structure-based drug design (SBDD) underwent a similar cycle. Early proponents oversold what could be achieved through SBDD, thereby causing pharmaceutical companies to reconsider their investments when they discovered that SBDD too was no panacea for filling the drug discovery cornucopia with choice molecules for development. Nevertheless, SBDD was an important advance. 

Kuntz ID. Structure-based strategies for drug design and discovery. Science 1992 257 1078-82. 

Tondi D, Costi MR Enhancing the drug discovery process by integration of structure-based design and combinatorial synthesis. In Viswanadhan AK, Chose VN, editors. Combinatorial library design and evaluation. New York Marcel Dekker, 2001. p. 563-604. 

Murray CW, Clark DE, Auton TR, Firth MA, Li J, Sykes RA, Waszkowycz B, Westhead DR, Young SC. PRO SELECT combining structure-based drug design and combinatorial chemistry for rapid lead discovery. J Comput Aided Mol Des 1997 11 193-207. 

Salemme FR, Spurlino J, Bone R. Serendipity meets precision the integration of structure-based drug design and combinatorial chemistry for efficient drug discovery. Structure 1997 5 319-324. 

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