title: Chemogenomic approaches to rational drug design.
abstract: Paradigms in drug design and discovery are changing at a significant pace. Concomitant to the sequencing of over 180 several genomes, the high-throughput miniaturization of chemical synthesis and biological evaluation of a multiple compounds on gene/protein expression and function opens the way to global drug-discovery approaches, no more focused on a single target but on an entire family of related proteins or on a full metabolic pathway. Chemogenomics is this emerging research field aimed at systematically studying the biological effect of a wide array of small molecular-weight ligands on a wide array of macromolecular targets. Since the quantity of existing data (compounds, targets and assays) and of produced information (gene/protein expression levels and binding constants) are too large for manual manipulation, information technologies play a crucial role in planning, analysing and predicting chemogenomic data. The present review will focus on predictive in silico chemogenomic approaches to foster rational drug design and derive information from the simultaneous biological evaluation of multiple compounds on multiple targets. State-of-the-art methods for navigating in either ligand or target space will be presented and concrete drug design applications will be mentioned.
authors.affiliation: Bioinformatics of the Drug, Centre National de la Recherche Scientifique UMR 7175-LC1, F-67400 Illkirch, France. didier.rognan@pharma.u-strasbg.fr
authors.forename: D
authors.initials: D
authors.lastname: Rognan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017076:Computer-Aided Design; D015195:Drug Design; D053263:Gene Regulatory Networks; D023281:Genomics; D006801:Humans; D021621:Imaging, Three-Dimensional; D008024:Ligands; D053858:Metabolic Networks and Pathways; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D008970:Molecular Weight; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D040681:Structural Homology, Protein; D049490:Systems Biology
chemical_list: D008024:Ligands