Theoretical understanding of macromolecular electrostatics
- Continuum models have given promising results for calculating protein–ligand binding free energy differences, as well as pKas and redox properties, particularly with explicit treatment of multiple conformers.
- The low computational cost and wide availability of continuum models, especially coupled to computer graphics, have made them household items in structural biology groups.
- Comparisons between continuum and microscopic descriptions of dielectric relaxation are a fruitful route for understanding the limitations of continuum models and finding ways to improve them. In one case, it was shown that different protein dielectric constants were required to describe static fields and field shifts induced by a perturbing charge. This indicates that, in some current applications, the charge set and dielectric constants may not be mutually consistent. Spatial eterogeneity of the solute dielectric properties is another, distinct effect that undoubtedly plays a role in many systems.
[Thomas Simonson, Laboratory for Structural Biology and Genomics, CNRS, IGBMC, France.https://www.sciencedirect.com/science/article/abs/pii/S0959440X00001974