A novel approach for assessing macromolecular complexes combining soft-docking calculations with NMR data

We present a novel and efficient approach for assessing protein-protein com plex formation, which combines ab initio docking calculations performed wit h the protein docking algorithm BiGGER and chemical shift perturbation data collected with heteronuclear single quantum coherence (HSQC) or TROSY nucl ear magnetic resonance (NMR) spectroscopy. This method, termed "restrained soft-docking," is validated for several known protein complexes. These data demonstrate that restrained soft-docking extends the size limitations of N MR spectroscopy and provides an alternative method for investigating macrom olecular protein complexes that requires less experimental time, effort, an d resources. The potential utility of this novel NMR and simulated docking approach in current structural genomic initiatives is discussed.