Accurate and rapid docking of protein-protein complexes on the basis of intermolecular nuclear overhauser enhancement data and dipolar couplings by rigid body minimization.
A simple and rapid method is presented for solving the three-dimensional structures of protein-protein complexes in solution on the basis of experimental NMR restraints that provide the requisite translational (i.e., intermolecular nuclear Overhauser enhancement, NOE, data) and orientational (i.e., backbone (1)H-(15)N dipolar couplings and intermolecular NOEs) information. Providing high-resolution structures of the proteins in the unbound state are available and no significant backbone conformational changes occur upon complexation (which can readily be assessed by analysis of dipolar couplings measured on the complex), accurate and rapid docking of the two proteins can be achieved. The method, which is demonstrated for the 40-kDa complex of enzyme I and the histidine phosphocarrier protein, involves the application of rigid body minimization using a target function comprising only three terms, namely experimental NOE-derived intermolecular interproton distance and dipolar coupling restraints, and a simple intermolecular van der Waals repulsion potential. This approach promises to dramatically reduce the amount of time and effort required to solve the structures of protein-protein complexes by NMR, and to extend the capabilities of NMR to larger protein-protein complexes, possibly up to molecular masses of 100 kDa or more.
Clore
G M
GM
Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0510, USA. clore@speck.niddk.nih.gov
D009682:Magnetic Resonance Spectroscopy; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
D011506:Proteins