Jed W. Pitera

Dielectric properties of proteins from simulation: the effects of solvent, ligands, pH, and temperature.

We have used a standard Fröhlich-Kirkwood dipole moment fluctuation model to calculate the static dielectric permittivity, epsilon(0), for four different proteins, each of which was simulated under at least two different conditions of pH, temperature, solvation, or ligand binding. For the range of proteins and conditions studied, we calculate values for epsilon(0) between 15 and 40. Our results show, in agreement with prior work, that the behavior of charged residues is the primary determinant of the effective permittivity. Furthermore, only environmental changes that alter the properties of charged residues exert a significant effect on epsilon. In contrast, buried water molecules or ligands have little or no effect on protein dielectric properties.

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.