ITR/AP (BIO) Computational tools for determining the 3-D static and dynamic structure of viruses

ITR/AP (BIO) 用于确定病毒 3D 静态和动态结构的计算工具

• 批准号: 0112672
• 负责人: Peter Doerschuk
• 金额: $ 35.93万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-10-01 至 2006-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0112672&HistoricalAwards=false
• 关键词: ITR; AP; BIO; Computational; tools

ITR Proposal 0112672, DoerschukAbstractUnderstanding the dynamical behavior of virus particles, e.g., the self assembly and subsequent maturation steps that lead to an infectious virus particle, is a key challenge in basic biology (e.g., the understanding of protein-nucleic acid interactions) and in medicine (e.g., the development of drugs that interfere with viral replication). This research contributes to that goal by developing new computational tools for structural biology, emphasizing experimental approaches appropriate for the study of dynamics and emphasizing the bi-directional interplay of new structural biology problems and new formulations of existing structural biology problems with the development of new computational tools.Models and computation for new types of experiments are under development, e.g., x-ray scattering from solutions of labeled viral particles which are oriented by immersion in a strong electric field thereby transforming solution scattering to something analogous to the more informative fiber diffraction. New computational approaches to standard problems are also under development, e.g., phase retrieval for the x-ray crystallography of particles with non-crystallographic symmetries based on iterative phase retrieval algorithms applied to lattices that are computationally oversampled by interpolators based on the symmetry. Computational areas involved include fast 3-D Radon transform algorithms, a component of computing the cryo electron micrograph predicted from a given virus structure, and global optimization, in order to improve the values of the parameters that describe the virus structure.The PIs have a long term interest in undergraduate involvement in research and financial support for undergraduate research assistants is included.

ITR 提案 0112672，Doerschuk 摘要了解病毒颗粒的动态行为，例如导致感染性病毒颗粒的自组装和随后的成熟步骤，是基础生物学（例如，了解蛋白质-核酸相互作用）和医学（例如，干扰病毒复制的药物的开发）。 这项研究通过开发新的结构生物学计算工具，强调适合动力学研究的实验方法，并强调新结构生物学问题和现有结构生物学问题的新表述与新计算方法的发展之间的双向相互作用，为实现这一目标做出了贡献。新型实验的模型和计算正在开发中，例如，标记病毒颗粒溶液的 X 射线散射，这些颗粒通过浸没在强电场中进行定向，从而将溶液散射转化为类似于信息更丰富的纤维的东西衍射。 针对标准问题的新计算方法也在开发中，例如，基于迭代相位检索算法的非晶体学对称性粒子的 X 射线晶体学相位检索，该算法应用于由基于对称性的插值器计算过采样的晶格。 涉及的计算领域包括快速 3-D Radon 变换算法（计算从给定病毒结构预测的冷冻电子显微照片的组件）和全局优化，以提高描述病毒结构的参数值。PI 具有包括对本科生参与研究的长期兴趣以及对本科生研究助理的财政支持。