Representativity of target families in the Protein Data Bank: impact for family-directed structure-based drug discovery.
Analysis of the population of enzyme structures in the Protein Data Bank across all levels of the functional classification based on enzyme commission (EC) numbers reveals that, in spite of the almost exponential growth in the number of structures deposited, progress in achieving complete occupancy at all EC levels is relatively slow. Moreover, inspection of the distribution of the population among the members of the different enzyme families uncovers a strong bias towards enzymes widely recognized as therapeutically relevant targets. The low representativity levels identified in some target families warn on the current scope and applicability of structure-based approaches to family-directed strategies in drug discovery.
Mestres
Jordi
J
Chemogenomics Laboratory, Research Unit on Biomedical Informatics, Institut Municipal d'Investigació Mèdica and Universitat Pompeu Fabra, 08003 Barcelona, Catalonia, Spain. jmestres@imim.es
D030562:Databases, Protein; D015195:Drug Design; D004798:Enzymes / Q000737:chemistry / Q000145:classification*; D011487:Protein Conformation
D004798:Enzymes