Protein structure determination by combining sparse NMR data with evolutionary couplings

Accurate determination of protein structure by NMR spectroscopy is challenging for larger proteins, for which experimental data are often incomplete and ambiguous. Evolutionary sequence information together with advances in maximum entropy statistical methods provide a rich complementary source of structural constraints. We have developed a hybrid approach (evolutionary coupling-NMR spectroscopy; ECEC-NMR) combining sparse NMR data with evolutionary residue-residue couplings and demonstrate accurate structure determination for several proteins 6-41 kDa in size.