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

Values of (3)J-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 (3)J-coupling values (4-8 Hz) to the averaging period that must cover the conformational variability of the torsional angle related to the (3)J-coupling, and due to the difficulty of handling the multiple-valued character of the inverse Karplus relation between torsional angle and (3)J-coupling. Both problems can be solved by using (3)J-coupling time-averaging local-elevation restraining MD simulation. Application to the protein hen egg white lysozyme using 213 backbone and side-chain (3)J-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 (3)J-coupling data in protein structure determination.

Automated summary

Experimental (3)J-coupling values derived from NMR on proteins are not straightforward for protein structure determination due to sensitivity and possibility of multiple values. However, by using a specific MD simulation method, it is possible to obtain a conformational ensemble compatible with experimental data, considering averaging and the algorithm's ability to escape local minima.