Advanced Protein Electrostatic

Our works paved the way for quantitative studies of electrostatic energies in proteins. We provided the first treatments that considered the entire contributions to electrostatic free energies of proteins1 and also introduced the first simplified microscopic treatment of the energy of charges in solvated proteins1 and the first free energy perturbation study of a charge in a protein2. Our models open the way to realistic calculations of pKa's, redox potentials and absolute binding energies in proteins (for reviews see 3,4). Our concepts about the energetics of charges in protein interiors and the meaning of dielectric constants5 are now widely used. Our works have arguably provided by far the most physical connection between microscopic and macroscopic formulations through the PDLD/S-LRA formulations. Having the different levels of elctrostsic treatments in our program packages has allow us to address key electrostatic proteins in an extremely powerful and reliable way. Our research continues to push the frontiers of quantifying and understanding electrostatic energies in proteins and other biological systems, as can be realized by looking at other items in this research description.

The three main options for representing the solvent in computer simulation approaches. The microscopic model uses detailed all-atom representation and evaluates the average interaction between the solvent residual charges and the solute charges. Such calculations are expensive. The simplified microscopic model replaces the time average dipole of each solvent molecule by a point dipole, while the macroscopic model is based on considering a collection of solvent dipoles in a large volume element.