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

了解病毒颗粒的动力学行为，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，理解蛋白质-核酸相互作用）和医学（例如，开发干扰病毒复制的药物）的关键挑战。本研究通过开发新的结构生物学计算工具，强调适用于动力学研究的实验方法，并强调新的结构生物学问题和现有结构生物学问题的新公式与新计算工具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，这些溶液通过浸泡在强电场中定向，从而将溶液散射转化为类似于更有用的纤维衍射的东西。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对称粒子的x射线晶体学的相位检索，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，这是计算从给定病毒结构预测的低温电子显微图的一个组成部分，以及全局优化，以便改进描述病毒结构的参数值。pi对本科生参与研究有长期兴趣，并包括对本科生研究助理的财政支持。

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.