Macromolecular electrostatics: continuum models and their growing pains

Theoretical understanding of macromolecular electrostatics has advanced sub stantially over the past year. Continuum models have given promising result s for calculating protein-ligand binding free energy differences, as well a s pK(a)s and redox properties, particularly with explicit treatment of mult iple conformers. Generalized Born and other techniques have led to the firs t molecular dynamics simulations of proteins and RNA with continuum solvent . Continuum and microscopic descriptions of dielectric relaxation have been critically compared.