For several years, the David H. Murdock Research Institute (DHMRI) and a pharmaceutical company collaborated closely to perform high-volume screening of ligands binding to proteins of interest. The company initially chose DHMRI to conduct these experiments because of the institute’s ability to process a high number of samples at one time, and the flexibility to accommodate an uninterrupted run of samples over several days.
Using the 480-sample capacity of the SampleJet autosampler available on a 700 MHz NMR spectrometer, 600 different ligand/protein combinations were screened using Saturation Transfer Difference experiments. Interesting binding candidates were then tested with a 15N labeled protein using HSQC experiments to determine the location of the binding on the protein.
This initial project has led to several follow-on studies that take advantage of DHMRI’s expertise, capacity and flexibility to run similar high-volume experiments.