Property-based design of GPCR-targeted library.
The design of a GPCR-targeted library, based on a scoring scheme for the classification of molecules into "GPCR-ligand-like" and "non-GPCR-ligand-like", is outlined. The methodology is a valuable tool that can aid in the selection and prioritization of potential GPCR ligands for bioscreening from large collections of compounds. It is based on the distillation of knowledge from large databases of GPCR and non-GPCR active agents. The method employed a set of descriptors for encoding the molecular structures and by training of a neural network for classifying the molecules. The molecular requirements were profiled and validated by using available databases of GPCR- and non-GPCR-active agents [5736 diverse GPCR-active molecules and 7506 diverse non-GPCR-active molecules from the Ensemble Database (Prous Science, 2002)]. The method enables efficient qualification or disqualification of a molecule as a potential GPCR ligand and represents a useful tool for constraining the size of GPCR-targeted libraries that will help speed up the development of new GPCR-active drugs.
Balakin
Konstantin V
KV
Chemical Diversity Labs, Inc., 11575 Sorrento Valley Road, San Diego, California 92121, USA. kvb@chemdiv.com
Tkachenko
Sergey E
SE
Lang
Stanley A
SA
Okun
Ilya
I
Ivashchenko
Andrey A
AA
Savchuk
Nikolay P
NP
D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D008024:Ligands; D015394:Molecular Structure; D016571:Neural Networks, Computer; D019151:Peptide Library; D011956:Receptors, Cell Surface / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015203:Reproducibility of Results
D008024:Ligands; D019151:Peptide Library; D011956:Receptors, Cell Surface; D020962:Heterotrimeric GTP-Binding Proteins