The NMR functional chemical library is a new type of compound library that focuses on aiding in the functional annotation of novel proteins that have been identified from various ongoing genomics efforts. The NMR functional chemical library is an integral component of our FAST-NMR assay. The NMR functional chemical library is comprised of small molecules with known biological activity such as: amino acids, carbohydrates, co-factors, hormones, inhibitors, known drugs, lipids, metabolites, neurotransmitters, nucleotides, substrates and vitamins.

This functional library was developed through an extensive manual effort of mining several databases based on known ligand interactions with protein systems.  In order to increase the efficiency of screening the NMR functional library, the compounds are screened as mixtures of 3-4 compounds that avoids the need to deconvolute positive hits by maintaining a unique NMR resonance and function for each compound in the mixture.

The compounds in the functional chemical library are known to bind to certain class of proteins. By identifying the types of ligands that bind a hypothetical protein, the cellular function of the ligand and the functional class of proteins known to bind the ligand can then be associated to the hypothetical protein or protein of unknown function.

A ChemFinder database was created that correlates the compounds in the functional library with protein-ligand co-structures in the PDB that contain the compound. The database also links to NMR spectra and contains descriptions of the compounds.

In addition to providing functional information for hypothetical proteins, positive "hits" from the library may provide a valuable starting point for a structure-based drug design effort since the compounds adhere to known "drug-like" characteristics and are known to be biologically active and available.

K. A. Mercier, K. Germer and R. Powers (2006) “Design and Characterization of a Functional Library for NMR Screening against Novel Protein Targets.”, Combinatorial Chemistry & High Throughput Screening, 9(7):515-534.

K. A. Mercier, M. Baran, V. Ramanathan, P. Revesz, R. Xiao, G. T. Montelione and R. Powers (2006) “FAST-NMR - Functional Annotation Screening Technology Using NMR.” Journal of the American Chemical Society, 128(47):15292-15299.

R. Powers, J. Copeland and K. Mercier (2008) “The Application of FAST-NMR for the Identification of Novel Drug Discovery Targets.”, Drug Discovery Today, 13(3-4):172-179.