Protein structure determination by combining sparse NMR data with evolutionary couplings

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