On the use of 3J-coupling NMR data to derive structural information on proteins

Values of ³J-couplings as obtained from NMR experiments on proteins cannot easily be used to determine protein structure due to the difficulty of accounting for the high sensitivity of intermediate ³J-coupling values (4–8?Hz) to the averaging period that must cover the conformational variability of the torsional angle related to the ³J-coupling, and due to the difficulty of handling the multiple-valued character of the inverse Karplus relation between torsional angle and ³J-coupling. Both problems can be solved by using ³J-coupling time-averaging local-elevation restraining MD simulation. Application to the protein hen egg white lysozyme using 213 backbone and side-chain ³J-coupling restraints shows that a conformational ensemble compatible with the experimental data can be obtained using this technique, and that accounting for averaging and the ability of the algorithm to escape from local minima for the torsional angle induced by the Karplus relation, are essential for a comprehensive use of ³J-coupling data in protein structure determination.