An accurate and rapid computational method for predicting reaction rates for biochemical processes would be developed as a tool for biochemistry research. Existing semiempirical methods, while rapid, are not sufficiently accurate. The recently completed PM6 method has increased the accuracy of prediction of heats of formation of stable ground-state systems, but is still not accurate for predicting transition state energies. The proposed work would involve developing a method specifically designed for predicting activation barriers. This would involve the construction of a database of activation barriers. Existing semiempirical methods use a consistent set of parameters in predicting geometries and energies. In the new approach, Geometries would be predicted using PM6, and energies would be less elegant than conventional methods it would allow activation barriers to be predicted with much better accuracy. Construction of the database of activation barriers would involve using results of very high-level ab-initio calculations. Other groups have done calculations of this type, so this step would involve only literature research. Development of the new method involves parameter optimization only. The issues involved are now well understood, and available optimization programs should be sufficient. Finally, the new method would be integrated into existing commercial program MOPAC2009, which would be re-named MOPAC2011.
The work to be done involves developing a method to predict accurately the size of reaction barriers, giving an indication of which biochemical processes are feasible.
| Stewart, James J P (2013) Optimization of parameters for semiempirical methods VI: more modifications to the NDDO approximations and re-optimization of parameters. J Mol Model 19:1-32 |
| Dutra, José Diogo L; Filho, Manoel A M; Rocha, Gerd B et al. (2013) Sparkle/PM7 Lanthanide Parameters for the Modeling of Complexes and Materials. J Chem Theory Comput 9:3333-3341 |
