A novel interactive tool for rigid-body modeling of multi-domain macromolecules using residual dipolar couplings

Residual dipolar couplings (RDC), measured by dissolving proteins in dilute liquid crystal media, or by studying naturally paramagnetic molecules, hav e rapidly become established as routine measurements in the investigation o f the structure of macromolecules by NMR. One of the most obvious applicati ons of the previously inaccessible long-range angular information afforded by RDC is the accurate definition of domain orientation in multi-module mac romolecules or complexes. In this paper we describe a novel program develop ed to allow the determination of alignment tensor parameters for individual or multiple domains in macromolecules from residual dipolar couplings and to facilitate their manipulation to construct low-resolution models of macr omolecular structure. For multi-domain systems the program determines the r elative orientation of individual structured domains, and provides graphica l user-driven rigid-body modeling of the different modules relative to the common tensorial frame. Translational freedom in the common frame, and equi valent rotations about the diagonalized (x,y,z) axes are used to position t he different modules in the common frame to find a model in best agreement with experimentally measured couplings alone or in combination with additio nal experimental or covalent information.