A target function for quaternary structural refinement from small angle scattering and NMR orientational restraints

We present a novel target function based on atomic coordinates that permits quaternary structural refinement of multi-domain protein–protein or protein–RNA complexes. It requires that the high-resolution structures of the individual domains are known and that small angle scattering (SAS) data as well as NMR orientational restraints from residual dipolar couplings (RDCs) of the complex are available. We show that, when used in combination, the translational and rotational restraints contained in SAS intensities and RDCs, respectively, define a target potential function that permits to determine the overall topology of complexes made up of domains with low internal symmetry. We apply the target function on a modestly anisotropic model system, the Barnase/Barstar complex, and discuss factors that influence the structural refinement such as data errors and the geometrical properties of the individual domains.