Conformation mining: an algorithm for finding biologically relevant conformations.
Discovering essential features shared by active compounds, an important step in drug-design, is complicated by conformational flexibility. We present a new algorithm to efficiently mine the conformational space of multiple actives and find small subsets of conformations likely to be biologically relevant. The approach identifies chemical and steric similarities between actives, providing insight into features important for binding when structural data are absent. Validation studies (thrombin and CDK2 data) produce alignments similar to protein-based alignments.
Putta
Santosh
S
Rational Discovery LLC, 555 Bryant Street #467, Palo Alto, California 94301, USA. sputta@rationaldiscovery.com
Landrum
Gregory A
GA
Penzotti
Julie E
JE
D000465:Algorithms; D042846:CDC2-CDC28 Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry; D018360:Crystallography, X-Ray; D051357:Cyclin-Dependent Kinase 2; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011506:Proteins / Q000737:chemistry*; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000737:chemistry
D008024:Ligands; D011506:Proteins; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D013917:Thrombin