Molecular dynamics and accuracy of NMR structures: Effects of error boundsand data removal

The effect of internal dynamics on the accuracy of nuclear magnetic resonan ce (NMR) structures was studied in detail using model distance restraint se ts (DRS) generated from a 6.6 nanosecond molecular dynamics trajectory of b ovine pancreatic trypsin inhibitor. The model data included the effects of internal dynamics in a very realistic way. Structure calculations using dif ferent error estimates were performed with iterative removal of systematica lly violated restraints. The accuracy of each calculated structure was meas ured as the atomic root mean square (RMS) difference to the optimized avera ge structure derived from the trajectory by structure factors refinement. M any of the distance restraints were derived from NOEs that were significant ly affected by internal dynamics. Depending on the error bounds used, these distance restraints seriously distorted the structure,leading to deviation s from the coordinate average of the dynamics trajectory even in rigid regi ons. Increasing error bounds uniformly for all distance restraints relieved the strain on the structures. However, the accuracy did not improve. Signi ficant improvement of accuracy was obtained by identifying inconsistent res traints with violation analysis, and excluding them from the calculation. T he highest accuracy was obtained by setting bounds rather tightly, and remo ving about a third of the restraints. The limiting accuracy for all backbon e atoms was between 0.6 and 0.7 Angstrom. Also, the precision of the struct ures increased with removal of inconsistent restraints, indicating that a h igh precision is not simply the consequence of tight error bounds but of th e consistency of the DRS, The precision consistently overestimated the accu racy. Proteins 1999;34:453-463. (C) 1999 Wiley-Liss, Inc.