Comp Chem Research Developments

December 12, 2005

Improvement of charge-dependent response properties in semiempirical QM/MM models for RNA catalysis

RNA systems are highly negatively charged and exhibit strong interactions with solvent and metal ions.  These interactions are sensitive to electronic polarization effects, and are attenuated by local charge.  Semiempirical quantum models that are most typically used in hybrid quantum mechanical/molecular mechanical (QM/MM) simulations of RNA catalysis are limited in their accuracy due to systematically poor treatment of charge-dependent response properties, in particular polarizability.  One method to increase the reliability of these models would be to increase the size of the basis set in the molecular orbital expansion; however, this techniques would greatly increase the computational cost of the simulations by orders of magnitude.

Recently, Professor Darrin York and graduate student Timothy Giese have developed a method to greatly improve the semiempirical electronic response properties through a density-functional expansion method called chemical potential equalization (CPE).  The method does not significantly increase the computational cost of the calculations, and is therefore a very attractive alternative to much more expensive ab initio methods.  This development demonstrates a considerable advance in the arsenal of multi-scale computational models used to study highly charged reactive systems such as those encountered in RNA catalysis.

Figure 1. The polarizability of oxygen as a function of it's charge state (upper left) and a comparison of MNDO/d (black) and MNDO/d+CPE (red) isotropic polarizabilities with B3LYP/6-31++G(d,p) for neutral (upper right), monoanionic (lower left), and monocationic (lower right) molecules. Ref. are reference polarizabilities, MNDO are the polarizabilities predicted using the MNDO Hamiltonian. Ref.-MNDO is the difference between the reference and MNDO polarizabilities, i.e., the desired polarizability correction. Exp. Fit is an exponential function fit to the desired polarizability correction. Click on any image to enlarge.

The results have recently been published in a JCP article. These results make an important contribution toward the design of next-generation semiempirical quantum models for biological molecules that can be used in linear-scaling electronic structure and QM/MM simulations.