Structural interaction fingerprints: a new approach to organizing, mining, analyzing, and designing protein-small molecule complexes.
The combination of advances in structure-based drug design efforts in the pharmaceutical industry in parallel with structural genomics initiatives in the public domain has led to an explosion in the number of structures of protein-small molecule complexes structures. This information has critical importance to both the understanding of the structural basis for molecular recognition in biological systems and the design of better drugs. A significant challenge exists in managing this vast amount of data and fully leveraging it. Here, we review our work to develop a simple, fast way to store, organize, mine, and analyze large numbers of protein-small molecule complexes. We illustrate the utility of the approach to the management of inhibitor complexes from the protein kinase family. Finally, we describe our recent efforts in applying this method to the design of target-focused chemical libraries.
Computational Drug Design Group, Department of Research Informatics, Biogen Idec, 12 Cambridge Center, Cambridge, MA 02142, USA.
Juswinder
J
Singh
Zhan
Z
Deng
Gaurav
G
Narale
Claudio
C
Chuaqui
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017124:Conserved Sequence; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D008024:Ligands; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases