Computer modeling of Biochemical Reaction Rates

描述（由申请人提供）：将开发一种准确快速的预测生化过程反应速率的计算方法，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生成热预测的准确性，但在预测过渡态能量方面仍然不够准确。有目的的工作将包括开发一种专门用于预测激活屏障的方法。这将涉及到激活屏障数据库的构建，并使用该数据库来优化参数以重现激活屏障。现有的半经验方法使用一组一致的参数来预测几何形状和能量。在新方法中，将使用PM6预测几何形状，并使用所提出的方法预测能量。尽管这两步程序不如传统方法简单，但它可以更准确地预测激活障碍。激活势垒数据库的构建将涉及使用非常高级别的从头计算的结果。其他小组已经做过这种类型的计算，所以这一步只需要文献研究。新方法的开发只涉及参数优化。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，新方法将集成到现有的商业计划MOPAC2007中。

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 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 purposed work would involve developing a method specifically designed for predicting activation barriers. This would involve the construction of a database of activation barriers, and using that database to optimize parameters to reproduce the 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 predicted using the proposed method. Although this two-step procedure would be less elegant than conventional methods if would allow activation barriers to be predicted with much better accuracy. Construction of the database of activation barriers would involve using results over very high-level ab-initio calculations. Other groups have already 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 the existing commercial program MOPAC2007.