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Macromolecular Crystallography As A Tool For Investigating Drug, Enzyme And Receptor Interactions
Author(s) -
Oakley Aaron J,
Wilce Matthew Cj
Publication year - 2000
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2000.03215.x
Subject(s) - drug discovery , computational biology , drug , drug design , chemistry , protein structure , process (computing) , computer science , bioinformatics , biochemistry , biology , pharmacology , operating system
SUMMARY 1. Protein crystallography is an essential tool for the discovery and investigation of pharmacological interactions at the molecular level. It allows investigators to directly visualize the three‐dimensional structures of proteins, including enzymes, receptors and hormones. 2. Increasingly, knowledge of these interactions is being used in the drug‐discovery process. This is popularly called structure‐based drug design. The desired drug could be an enzyme inhibitor or an agonist that mimics endogenous transmitters or hormones. 3. Once the 3‐D structure of a pharmacologically relevant target is known, computational processes can be used to search databases of compounds to identify ones that may interact strongly with the target. Lead compounds can be improved using the 3‐D structure of the complex of the lead compound and its biological target. 4. The present review describes the processes involved in the determination of a structure by means of protein crystallography and the use of structures in the drug‐discovery process. A number of successful examples of structure‐based drug design are described. The limitations of the techniques are discussed.