Recent Research Developments
|Index of Recent Research News|
November 24, 2004
The study of biochemical reactions using combined quantum
mechanical (QM/MM) methods has gained tremendous attention.
Biological reactions occur in a complex solvated macromolecular
environment where electrostatic effects play are often attributed as
being a main source of
catalytic activity. The challenge in theoretical studies of
biochemical mechanisms is to move accurate quantum electronic
structure calculations from the gas phase into complex biological
environments. A key step toward this end involves the accurate
and efficient modeling of electrostatic interactions for these very
Recently, the research group of Prof. Darrin York
of the Department of Chemistry
has made several advances in the design of new methods to treat long
range electrostatic interactions in QM/MM simulations of biochemical
reactions. Prof. Darrin York, along with graduate student Brent
Gregersen have recently introduced a new method for treatment of
long-ranged electrostatic interactions in QM/MM stochastic
boundary molecular dynamics (SBMD) simulations. The method allows
the electrostatic environment due to a tremendously large system to be
accurately modeled in an enzyme's active site for a fraction of the
computational cost of direct methods (Figure 1). The first
publication on the Variational Electrostatic Projection (VEP) method
is currently in press in
the Journal of
Physical Chemistry B.
In some instances, it is important to apply more rigorous full periodic boundary simulations with explicit solvent. Although for molecular mechanical force field models, linear-scaling electrostatic methods for periodic systems exist, these methods have been sluggish in being generalized to combined QM/MM potentials due to the added complexity of the quantum mechanical electron density. Recently, Professor York, along with graduate student Kwangho Nam and Prof. Jiali Gao have developed a linear-scaling Ewald method for combined QM/MM simulations. Application of the linear-scaling QM/MM-Ewald method (Figure 2) demonstrates the importance of rigorous treatment of electrostatic interactions of reactions, especially those that involve ionic transition states or intermediates. The linear-scaling QM/MM-Ewald method is in press and is scheduled to appear in the first issue of the new ACS journal, Journal of Chemical Theory and Computation, in January, 2005.
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Next scheduled update: Dec. 8, 2004.
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