Solvent Dielectric Effects on Protein Dynamics

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-06, Vol.89 (11), p.5167-5170
• Main Authors: Affleck, Rhett, Haynes, Charles A., Clark, Douglas S.
• Format: Article
• Language: English
• Subjects: alpha -chymotrypsin; Amino acids; Atoms; Biochemistry; Biological and medical sciences; Chymotrypsin - chemistry; Computer Simulation; Conformational dynamics in molecular biology; dielectric constant; Dielectric materials; dynamics; E.S.R; Electron Spin Resonance Spectroscopy; Electrostatics; Enzymes; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Methionine - chemistry; Models, Molecular; Molecular biophysics; Motion; Permittivity; Protein Conformation; Proteins; Rotational spectra; Serine - chemistry; Solvents; Solvents - chemistry; Spectral correlation; Spin Labels
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.11.5167

Electron paramagnetic resonance (EPR) spectroscopy and molecular dynamics (MD) simulations were used to investigate the dynamics of α-chymotrypsin in solvents ranging in dielectric constant from 72 to 1.9. EPR measurements showed that motions in the vicinity of two spin-labeled amino acids (Met-192 and Ser-195) decreased dramatically with decreasing solvent dielectric constant, a trend consistent with changes in the electrostatic force between charged residues of the protein. EPR results and MD simulations revealed a very similar functional dependence between rates of motion in the protein and the dielectric constant of the bulk solvent; however, predicted motions of protein atoms were markedly faster than measured motions of the spin labels. MD calculations for dielectric constants of 5 and 72 showed the greatest differences near the outer surface of the protein. In general, at the lower dielectric constant many atoms of the protein move more slowly, and many of the slowest residues are near the exterior. These results suggest that altered dynamics may contribute to the unusual properties-e.g., modified stereoselectivities-of enzymes in nearly dry organic solvents.