Open AccessStructural genomics and drug discovery
Author(s) -
Lundstrom K.
Publication year - 2007
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2007.00028.x
Subject(s) - structural genomics , drug discovery , computational biology , genomics , genome , drug , structural biology , biology , protein structure , bioinformatics , gene , genetics , biochemistry , pharmacology
• Background to drug discovery • Structure determination and drug discovery • Expression systems ‐ Cell‐free translation ‐ Bacterial expression ‐ Expression in E. coli‐ Other prokaryotic systems‐ Expression in yeast cells ‐ Expression in insect cells ‐ Baculovirus ‐ Other insect vectors‐ Expression in mammalian cells ‐ Transient and stable expression ‐ Viral vectors• Protein purification • Structure determination ‐ X‐ray crystallography ‐ Nuclear magnetic resonance ‐ Electron microscopy ‐ Structural genomics programs• Conclusions and future prospectsAbstract Structure determination has already proven useful for lead optimization and direct drug design. The number of high‐resolution structures available in public databases today exceeds 30,000 and will definitely aid in structure‐based drug design. Structural genomics approaches covering whole genomes, topologically similar proteins or gene families are great assets for further progress in the development of new drugs. However, membrane proteins representing 70% of current drug targets are poorly characterized structurally. The problems have been related to difficulties in obtaining large amount of recombinant membrane proteins as well as their purification and structure determination. Structural genomics has proven successful in developing new methods in areas from expression to structure determination by studying a large number of target proteins in parallel.