Distance‐dependent dielectric constants and their application to double‐helical DNA

Detailed studies of structures of biological macromolecules, even in simplified models, involve many costly and time‐consuming calculations. Any thorough methods require sampling of an extremely large conformation and momentum space. Calculations of electrostatic interactions, which depend on many physical factors, such as the details of solvent, solvent accessibility in macromolecules, and molecular polarizability, are always developed in a compromise between more rigorous, detailed models and the need for immediate application to complicated biological systems. In this paper, a middle ground is taken between the more exact theoretical models and the simplest constant values for the dielectric constant. The effects of solvent, counterions, and molecular polarizability are incorporated through a set of adjustable parameters that should be determined from experimental conditions. Several previous forms for the dielectric function are compared with the new ones. The present methods use Langevin functions to span the region of dielectric constant between bulk solvent and cavity values. Application of such dielectric models to double‐helical DNA is important because base‐stacking preferences were previously demonstrated [A. Sarai, J. Mazur, R. Nussinov, and R. L. Jernigan (1988) Biochemistry, vol. 27, pp. 8498–8502] to be sensitive to the electrostatic formulation. Here we find that poly (dG) · poly(dC) can be A form for high screening and B form for low screening. By contrast, poly (dA) · poly(dT) can only take the B form. Base stacking is more sensitive to the form of the dielectric function than are the sugar–phosphate backbone conformations. Also in B form, the backbone conformations are not so affected by the base types as in A form.