Assessing the effect of conformational averaging on the measured values of observables.
Experiment and computer simulation are two complementary tools to understand the dynamics and behavior of biopolymers in solution. One particular area of interest is the ensemble of conformations populated by a particular molecule 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 to determine the sensitivity of a particular experiment to changes in the distribution of molecular conformations. Consequently, a general analytic formalism is proposed to determine the sensitivity of a spectroscopic observable to the underlying distribution of conformations. A particular strength of the approach is that it provides an expression for a weighted average across 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 3J-coupling data on peptides in solution.
Bürgi
R
R
Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Zürich.
Pitera
J
J
van Gunsteren
W F
WF
D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015233:Models, Statistical; D008962:Models, Theoretical; D011487:Protein Conformation; D012680:Sensitivity and Specificity