Pharmacophore mapping via cross-relaxation during adiabatic fast passage

Author(s)
Renate Auer, Karin Kloiber, Andrea Vavrinska, Leonhard Geist, Nicolas Coudevylle, Robert Konrat
Abstract

A novel NMR method is demonstrated for the investigation of protein ligand interactions. In this approach an adiabatic fast passage pulse, i.e. a long, weak pulse with a linear frequency sweep, is used to probe 1H-1H NOEs. During the adiabatic fast passage the effective rotating-frame NOE is a weighted average of transverse and longitudinal cross-relaxation contributions that can be tuned by pulse power and frequency sweep rate. It is demonstrated that the occurrence of spin diffusion processes leads to sizable deviations from the theoretical relationship between effective relaxation rate and effective tilt angle in the spin lock frame and can be used to probe protein-ligand binding. This methodology comprises high sensitivity and ease of implementation. The feasibility of this technique is demonstrated with two protein complexes, vanillic acid bound to the quail lipocalin Q83 and NAD+ and AMP binding to alcohol dehydrogenase (ADH).

Organisation(s)
Department of Structural and Computational Biology, Department of Chromosome Biology
Journal
Journal of the American Chemical Society
Volume
132
Pages
1480-1481
No. of pages
2
ISSN
0002-7863
Publication date
2010
Peer reviewed
Yes
Austrian Fields of Science 2012
1040 Chemistry
Portal url
https://ucrisportal.univie.ac.at/en/publications/1adf5a05-953b-4a61-baa5-cd9ec822003f