Computational Modeling of Electrostatic Interactions in Biological Macromolecules

Experimental information about protein structure as well as energetics (such as binding free energies) are nowadays readily available. However it is difficult to connect structure with energy experimentally. Computer simulations necessarily connect structure with energy and thus can play a crucial role in the scientific quest to connect structure with function. However the role of simulations is limited by the accuracy of the force fields that model energy as a function of conformation, making the search for accurate but efficient force fields an important area of study. Electrostatic interactions represent the largest energy components in current force fields; thus improved modeling of electrostatic interactions is an important first step towards improved force fields. In this talk I will review previous work by our group and others directed at efficient but accurate representation of "long-range" electrostatics, and then discuss possible paths towards improved treatment of "short-range" electrostatics.