LINCOLN, Neb.—The hundreds of genome projects have led to thousands of protein structures dotting the database landscape. Unfortunately, sequence and structure information do not always indicate molecular function. Researchers at University of Nebraska and Rutgers University, however, recently combined NMR spectroscopy and bioinformatics to assign protein function.
As they reported in JACS, the researchers developed the functional annotation screening technology using NMR spectroscopy (FAST-NMR) to identify small-molecule ligands for different proteins. Upon combining compounds with proteins, they analyze the small molecules using 1-D NMR to look for line broadening, an indication of protein binding. They then analyze the protein using 2-D NMR to see which amino acids are closest to the ligand.
Using AutoDock, the researchers model the ligand binding site and screen the Comparison of Protein Active Site Structures (CPASS) database for proteins with similar binding characteristics, suggesting protein function. Using FAST-NMR, the researchers showed that the SAV1430 protein from S. aureus, which had no known function, was part of a multi-protein complex involved in signal transduction.