Assessing the effect of conformational averaging on the measured values ofobservables

Experiment and computer simulation are two complementary tools to understan d the dynamics and behavior of biopolymers in solution. One particular area of interest is the ensemble of conformations populated by a particular mol ecule in solution. For example, what fraction of a protein sample exists in its folded conformation? How often does a particular peptide form an alpha helix versus a beta hairpin? To address these questions, it is important t o determine the sensitivity of a particular experiment to changes in the di stribution of molecular conformations. Consequently, a general analytic for malism is proposed to determine the sensitivity of a spectroscopic observab le to the underlying distribution of conformations. A particular strength o f the approach is that it provides an expression for a weighted average acr oss conformational substates that is independent of the averaging function used. The formalism is described and applied to experimental and simulated nuclear Overhauser enhancement (NOE) and (3)J-coupling data on peptides in solution.