TRAJECTORY ANALYSIS OF NMR STRUCTURE CALCULATIONS

NMR as well as X-ray crystallography are used to determine the three-d imensional structures of macromolecules at atomic resolution. Structur e calculation generates coordinates that are compatible with NMR data from randomly generated initial structures. We analyzed the trajectory taken by structures during NMR structure calculation in conformationa l space, assuming that the distance between two structures in conforma tional space is the root-mean-square deviation between the two structu res. The coordinates of a structure in conformational space were obtai ned by applying the metric multidimensional scaling method. As an exam ple, we used a 22-residue peptide, mu-Conotoxin GIIIA, and a simulated annealing protocol of XPLOR. We found that the three-dimensional solu tion of the multidimensional scaling analysis is sufficient to describ e the overall configuration of the trajectories in conformational spac e. By comparing the trajectories of the entire calculation with those of the converged calculation, random sampling of conformational space is readily discernible. Trajectory analysis can also be used for optim ization of protocols of NMR structure calculation, by examining indivi dual trajectories.