How is an NMR structure best defined? An analysis of molecular dynamics distance-based approaches

Model studies on the macrocyclic immunosuppressive agent FK506 challenge traditional approaches to defining a structure from data collected during a 2D NMR experiment. A variety of joint molecular dynamics/NMR-distance refinement methodologies are characterized. From the results it is clear that the traditional presentation of an NMR structure as a single representative minimized conformation or as a fairly tight envelope of conformers best meeting the imposed restraints can be misleading; a greater emphasis is required on dynamics and on the fact that an NMR structure represents a time average.