The contribution of quantum mechanical solute polarization to the solvation free energies and electrostatic potential surfaces of biological macromolecules

In this report, results are presented for continuum electrostatic calculations of proteins and DNA (up to 10,000 atoms) in which the solute charge density is treated fully quantum-mechanically at the semi-empirical level using recently developed linear-scaling electronic structure methods. In this way, the contribution of solute polarization to the salvation free energy and electrostatic potential surfaces is directly assessed. Results indicate that for proteins this contribution is typically 10-20% of the total salvation free energy, and for DNA is around 2-5%. More importantly, solute polarization can have a considerable local affect on the electrostatic potential surface in highly polar regions such as protein active sites where there is a large degree of charge-charge interaction. The methodology presented provides a foundation for a host of applications to the quantum mechanical study of macromolecules in solution