NMR Structure Determination by Conformational Space Annealing

Abstract

We have carried out numerical experiments to investigate the applicability of global optimization method to the NMR structure determination. Since the number of NMR observables is relatively small in the early stage of NMR structure determination process and long range NOE observables are difficult to obtain, advanced sampling techniques are greatly in need to generate valid NMR structures from a small number of experimental restraints. By utilizing conformational space annealing method, we have determined solution NMR structures from NOE distance and backbone dihedral restraints. Several solution NMR structures are determined starting from fully randomized conformations. We have evaluated them by measuring the qualities of determined structures, such as structure convergence of ensemble, Ramachandran preferences, clash scores, and the total NOE violation. These qualities are compared to those from the corresponding PDB structures. When we applied the method to recent PDB deposits of 120 proteins ranging from 50 to 261 residues, we were able to generate protein structures which are superior to PDB structures in all four criteria for about 80% of the cases.