Computer Modeling of Biochemical Reaction Rates

描述（由申请人提供）：将开发一种用于预测生物化学过程反应速率的准确和快速的计算方法，作为生物化学研究的工具。现有的半经验方法虽然快速，但不够准确。最近完成的PM6方法提高了稳定基态系统的生成热预测的准确性，但仍然是不准确的预测过渡态能量。拟议的工作将涉及开发一种专门用于预测激活障碍的方法。这将涉及建立一个激活障碍数据库。现有的半经验方法在预测几何形状和能量时使用一组一致的参数。在新方法中，几何形状将使用PM6进行预测，并且能量将不如传统方法那么优雅，它将允许以更好的准确度预测激活势垒。活化障碍数据库的建设将涉及使用非常高层次的从头计算的结果。其他小组已经做过这类计算，所以这一步只涉及文献研究。新方法的开发仅涉及参数优化。所涉及的问题现在已经很好地理解了，可用的优化程序应该足够了。最后，新方法将被集成到现有的商业程序MOPAC2009中，该程序将被重新命名为MOPAC2011。 公共卫生相关性：要做的工作包括开发一种方法来准确地预测反应障碍的大小，给出一个指示，其中生化过程是可行的。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.