Computer Modeling of Biomolecular Systems

描述（由申请人提供）：提出了用于生物大分子的全量子力学建模的软件，该软件既快速又准确。癌症研究人员可以使用这个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。该软件将以半经验量子化学计算引擎为基础，新开发了包括六种主要过渡元素在内的所有生物元素的参数化。在第一阶段的提案中，将回答生物系统是否可以达到3 kcal/mol的准确度的问题。如果答案是肯定的，第二阶段将开展下列工作：将开发针对蛋白质和其他生物分子的方法。现有的方法（a）太一般，和（B）由于缺乏过渡金属而不适合于生物化学工作。通过开发特定于生物化学中发现的系统的半经验方法，可以获得准确性的增加，因此半经验方法的平均误差相对于PM 3应减少约60%。类似地，将过渡金属的优化性质范围限制在生化系统中发现的那些，将实现至少相当于从头算6- 31 g的准确度。B。编写图形用户界面（GUI）和实用程序，以允许反应，过渡态，紫外可见光谱等建模。这些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。计算引擎将以足以允许执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，并了解所涉及的机制。

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.