Computer Modeling of Biomolecular Systems

描述（由申请人提供）：提出了一种快速准确的生物大分子全量子力学建模软件。癌症研究人员可以使用该软件来模拟蛋白质和酶的结构，以及涉及键形成和断裂的酶反应。该软件将基于半经验量子化学计算引擎，具有新开发的所有生物元素参数化，包括六个主要过渡元素。在这个第一阶段的建议中，将回答生物系统是否可以达到3千卡/摩尔的精度的问题。如果这个答案是肯定的，第二阶段将进行以下任务：A.开发针对蛋白质和其他生物分子的方法。现有的方法(a)过于笼统，(b)由于缺乏过渡金属，不适合生化工作。通过开发针对生物化学中发现的系统的半经验方法，可以获得准确性的提高，因此，相对于PM3，半经验方法的平均误差应降低约60%。同样，将过渡金属优化的性质范围限制在生化系统中发现的性质范围内，将实现至少相当于从头计算6-31g的精度。B.编写图形用户界面（GUI）和实用程序，以允许对反应，过渡状态，紫外可见光谱等进行建模。这将允许用户通过发出“请求”来运行模拟，GUI将其转换为计算引擎的命令。计算引擎将以足以进行实时模拟的速度运行。这个工具将有助于可视化生化系统，并有助于理解所涉及的机制。

DESCRIPTION (provided by applicant): Software for full quantum mechanics modeling of biological macromolecules that is both fast and accurate is proposed. Cancer researchers could use this software to model protein and enzyme structure as well as enzyme reactions involving bond formation and breaking. The software would be based on a semi-empirical quantum chemical compute engine with a newly developed parameterization for all biological elements including the six principal transition elements. In this Phase I proposal, the question of whether an accuracy of 3 kcal/mol can be achieved for biological systems will be answered. If this answer is affirmative, the following tasks will be pursued in Phase II: A. Methods specific to proteins and other biomolecules would be developed. Existing methods are (a) too general, and (b) unsuitable for biochemical work, due to the lack of transition metals. By developing semiempirical methods that are specific to systems found in biochemistry, an increase in accuracy can be obtained, thus the average error in semiempirical methods should be decreased by about 60% relative to PM3. Similarly, limiting the range of properties optimized for transition metals to those found in biochemical systems, an accuracy at least equivalent to ab initio 6-31g would be achieved. B. Writing Graphical user interfaces (GUI) and utilities to allow reactions, transition states, UVVisible spectra, etc. to be modeled. These will allow users to run simulations using by issuing "requests", which the GUI will convert into commands for the compute engine. The compute engine would run at a speed sufficient to allow real-time simulations to be performed. This tool will be useful for visualizing biochemical systems, and for understanding the mechanisms involved.