Variational Electrostatic Projection (VEP) methods for efficient modeling of the macromolecular electrostatic and solvation environment in activated dynamics simulations

The Journal of Physical Chemistry B vol. 109  p. 536-556  DOI: 10.1021/jp0469968
PMID/PMCID: 16851046 Published: 2005-01-13 

Brent A. Gregersen, Darrin M. York [ ]

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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 Å 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.