Model building study of complex structures using NMR chemical shift change information

Upon tight binding of two molecules, it is frequently observed that NMR chemical shifts change significantly. We propose a novel method that incorporates this information in the model building procedure, so that the atomic model of the complex structure is built without human manipulation. When the chemical shift of an atom is changed significantly, we call it an active atom. Then, we have added a heuristic restraint in the simulated annealing procedure. It gives no penalty when the active atom of a molecule is near at least one of active atoms in the other molecule, but it imposes a large penalty when the active atom is far from the other molecule. The structures of the individual molecules are formed and maintained by the intramolecular distance restraints. Results are shown for a model of an SH3 domain with a polyproline peptide, in which the complex structure can be rebuilt with both a rigid and a flexible ligand peptide.