Computation for Structural Biology: Tools to Enable Dynamic 3-D Reconstruction of Time-varying Viral Structures

提案#0098156普渡大学研究基金会Doerschuk，Peter CA计算结构生物学的关键挑战是确定病毒的3-D结构，特别是3-D结构的动态变化，这对理解病毒的功能至关重要。 这些信息对于合理设计药物以对抗病毒感染和将病毒用于其他目的，例如，作为将药物靶向递送至特定器官的载体。 解决这些问题涉及到两个数值计算问题的新算法的开发、分析、实现和使用，这两个问题是全局优化和多维quadriumquadrium.The调查人员通过定位成本的全局最小值来计算3-D结构，该成本是实验数据和预测值的函数，并且量化数据和预测数据之间的差异。 预测，其评价需要多维正交，是一个函数的参数描述的3-D结构的病毒和任何未知方面的数据收集过程和最小化是相对于这些参数。 该方法的性能受到全局优化和求积工具的限制，因此这些工具是本研究的重点。 关键的全局优化问题是利用多尺度结构的数据和参数的成本，由于傅立叶变换的存在和精度和计算费用之间的权衡，由于嵌入式求积的成本评估。 关键的多维正交问题是不寻常的被积函数和积分区域，例如，在定义三维旋转的三个欧拉角上积分具有二十面体对称性的三个变量的函数。

Proposal #0098156Purdue Research FoundationDoerschuk, Peter CA key challenge in computational structural biology is the determination of the 3-D structure of a virus, andespecially dynamical changes in 3-D structure which are central to understanding the function of the virus. This information is central to rational design of drugs to combat viral infections and to the use of viruses for other purposes, e.g., as vehicles for the targeted delivery of drugs to specific organs. Solving these problems involves the development, analysis, implementation and use of new algorithms for two numerical computation problems, global optimization and multidimensional quadrature.The investigators compute a 3-D structure by locating the global minimum of a cost which is a function of experimental data and of a predictor, and which quantitates the difference between the data and the prediction of the data. The predictor, whose evaluation requires multidimensional quadrature, is a function of parameters describing the 3-D structure of the virus and any unknown aspects of the data collection process and the minimization is with respect to these parameters. Performance of the approach is limited bythe global optimization and quadrature tools and therefore these tools are the foci of this research. Key globaloptimization issues are exploiting the multi-scale structure of the data and parameters in the cost due to the presence of Fourier transforms and the tradeoff between accuracy and computational expense in the evaluation of the cost due to embedded quadratures. Key multidimensional quadrature issues are the unusual integrands and regions of integration, e.g., to integrate a function of three variables with icosahedral symmetry over the three Euler angles that define a 3-D rotation.