title: Assessing the effect of conformational averaging on the measured values of observables.
abstract: 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.
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Zürich.
authors.forename: R
authors.initials: R
authors.lastname: Bürgi
authors.forename: J
authors.initials: J
authors.lastname: Pitera
authors.forename: W F
authors.initials: WF
authors.lastname: van Gunsteren
mesh_terms: D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015233:Models, Statistical; D008962:Models, Theoretical; D011487:Protein Conformation; D012680:Sensitivity and Specificity