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A Quantum Description of Solvation

Posted by: Amanda Barnard

August 22, 2016

A QMC/MM model for imidazole in water.
A QMC/MM model for imidazole in water.

The acid dissociation constant (pKa) provides a direct measure deprotonation reactions, which are fundamentally important to chemistry and biochemistry. Unfortunately, experimental measurements of pKa in biological molecules is not straightforward, due to the solvent leveling effect and poor accessibility. For these and other reasons accruate theoretical methods are desperately needed for predicting pKa values in molecules.

Solvent and environment effects are fundamental to pKa calculations, but inclusion of these effects is prohibitive the use of accurate quantum mechanical methods like coupled cluster methods, many body perturbation theory or quantum Monte Carlo (QMC). Our solution to this challenge is to combine high-level quantum mechanical (QM) methods with low-level molecular mechanics methods (MM), and deliver a general QMC/MM method that is easy to use.  The advantage of describing the solute (and in some cases surrounding solvent molecules) is with QMC is that we retain the accuracy where it is needed most, while trading accuracy for speed in the solvent where classical forces dominate. Our focus is on the all-important interaction between the QMC and MM regions, and including polarization to enhance the accuracy of the short range interactions described by the MM region.

In this project, we are developing methods for accurately describing solvent and environment effects to calculate the pKa values based on QMC. This method will ultimately become a new solvation module in our CMQMC package, to allow the incorporation of polarizable and non-polarizable force fields, and the calculation of both acids and bases.

For more information, contact the Project Leader, Dr Nandun Thellamurege.