Determination of protein global folds using backbone residual dipolar coupling and long-range NOE restraints

We report the determination of the global fold of human ubiquitin using protein backbone NMR residual dipolar coupling and long-range nuclear Overhauser effect (NOE) data as conformational restraints. Specifically, by use of a maximum of three backbone residual dipolar couplings per residue (N-i-H-i(N), N-i-Ci-1' H-i(N)-Ci-1') in two tensor frames and only backbone H-N-H-N NOEs, a global fold of ubiquitin can be derived with a backbone root-mean-square deviation of 1.4 Angstrom with respect to the crystal structure. This degree of accuracy is more than adequate for use in databases of structural motifs, and suggests a general approach for the determination of protein global folds using conformational restraints derived only from backbone atoms.