USE OF TRANSFERRED NUCLEAR OVERHAUSER EFFECTS IN THE STUDY OF THE CONFORMATIONS OF SMALL MOLECULES BOUND TO PROTEINS

A novel method is proposed for the study of the conformation in solution of small molecules bound to proteins. In transfer of saturation experiments, irradiation at the frequency of a proton in the bound ligand can result in an intensity change in the signal from a different proton in the free excess ligand via a nuclear Overhauser effect between the two protons in the bound ligand. Approximatel calculations show that the observation of such effects depends upon the close spatial proximity (within about 4.0 Å) of the two protons involved and thus gives useful conformational information. Two examples of this method are given, for the binding of trimethoprim and NADP+, respectively, to Lactobacillus casei dihydrofolate reductase. © 1979.