The effect of protein relaxation on charge-charge interactions and dielectric constants of proteins.
The effect of the reorganization of the protein polar groups on charge-charge interaction and the corresponding effective dielectric constant (epsilon(eff)) is examined by the semimicroscopic version of the Protein Dipole Langevin Dipoles (PDLD/S) method within the framework of the Linear Response Approximation (LRA). This is done by evaluating the interactions between ionized residues in the reaction center of Rhodobacter sphaeroides, while taking into account the protein reorganization energy. It is found that an explicit consideration of the protein relaxation leads to a significant increase in epsilon(eff) and that semimicroscopic models that do not take this relaxation into account force one to use a large value for the so-called "protein dielectric constant," epsilon(p), of the Poisson-Boltzmann model or for the corresponding epsilon(in) in the PDLD/S model. An additional increase in epsilon(eff) is expected from the reorganization of ionized residues and from changes in the degree of water penetration. This finding provides further support for the idea that epsilon(in) (or epsilon(p)) represents contributions that are not considered explicitly. The present study also provides a systematic illustration of the nature of epsilon(eff), supporting our previously reported view that charge-charge interactions correspond to a large value of this "dielectric constant," even in protein interiors. It is also pointed out that epsilon(eff) for the interaction between ionizable groups in proteins is very different from the effective dielectric constant, epsilon'(eff), that determines the free energy of ion pairs in proteins (epsilon'(eff) reflects the effect of preoriented protein dipoles). Finally, the problems associated with the search for a general epsilon(in) are discussed. It is clarified that the epsilon(in) that reproduces the effect of protein relaxation on charge-charge interaction is not equal to the epsilon(in) that reproduces the corresponding effect upon formation of individual charges. This reflects fundamental inconsistencies in attempts to cast microscopic concepts in a macroscopic model. Thus one should either use a large epsilon(in) for charge-charge interactions and a small epsilon(in) for charge-dipole interactions or consider the protein relaxation microscopically.
Sham
Y Y
YY
Department of Chemistry, University of Southern California, Los Angeles 90089-1062, USA.
Muegge
I
I
Warshel
A
A
D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D007477:Ions; D008956:Models, Chemical; D045322:Photosynthetic Reaction Center Complex Proteins / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D012242:Rhodobacter sphaeroides / Q000737:chemistry; D055672:Static Electricity; D013816:Thermodynamics
D007477:Ions; D045322:Photosynthetic Reaction Center Complex Proteins; D011506:Proteins