title: Variational electrostatic projection (VEP) methods for efficient modeling of the macromolecular electrostatic and solvation environment in activated dynamics simulations.
abstract: New methods for the calculation of electrostatic interactions between the active dynamical region and surrounding external solvated macromolecular environment in hybrid quantum mechanical/molecular mechanical (QM/MM) simulations are presented. The variational electrostatic projection (VEP) method, and related variational reverse-mapping procedure (VEP-RVM) utilize an expansion in Gaussian surface elements for representation of electrostatic interactions. The use of a discretized surface that surrounds the active dynamical region greatly reduces the number of interactions with the particles of the external environment. The methods are tested on two catalytic RNA systems: the hammerhead and the hairpin ribozymes. It is shown that with surface elements numbering from 302 to 1202 points the direct VEP and VEP-RVM methods are able to obtain relative force errors in the range of 0.5-0.05% and 0.09-0.0001%, respectively, using a 4.0 A projection buffer. These results are encouraging and provide an essential step in the development of new variational macromolecular solvent-boundary methods for QM/MM calculations of enzyme reactions.
authors.affiliation: Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455-0431, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Gregersen
authors.forename: Darrin M
authors.initials: DM
authors.lastname: York
mesh_terms: D003198:Computer Simulation; D046911:Macromolecular Substances / Q000737:chemistry; D008956:Models, Chemical; D011789:Quantum Theory; D012997:Solvents / Q000737:chemistry; D055672:Static Electricity
chemical_list: D046911:Macromolecular Substances; D012997:Solvents