UNDERSTANDING THE DETERMINANTS OF VIRAL MATURATION USING FINITE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 A.目标 将进行大规模有限元连续溶剂化和静电学计算，以了解在病毒成熟过程中衣壳亚基间界面的电荷相互作用的作用。这项分析的结果将被用来通过计算预测衣壳亚单位界面突变的影响，以通过实验研究进行测试。特别是，我们提出了以下具体目标： 1.通过PKA预测和连续体系静电计算，模拟了Omega(N？V)和HK97噬菌体病毒成熟过程中电荷相互作用的影响。 2.将我们的静电建模框架集成到VIPERdb中病毒静电的大规模表征中，以开发用于病毒结构分析的新特征(http://viperdb.scripps.edu/)[1]。 拟议的目标建立在约翰逊实验室对N？v[2-11]和HK97[12-25]的现有实验工作以及McCammon、Baker和其他人[26，27]使用NBCR支持的工具APBS(http://apbs.sf.net/)[28]和PDB2PQR(http://pdb2pqr.sf.net/)[29，30])来探索病毒成熟过程中的衣壳静电学的过去研究的基础上。然而，这个合作项目将通过NBCR支持的工具FETK(http://www.fetk.org/)[32]提供的新的有限元网格生成技术[31]及其与APB的集成来显著扩展这项工作的范围。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A. Objectives Large scale finite element continuum solvation and electrostatics calculations will be performed to understand the role of charge-charge interactions at capsid inter-subunit interfaces during viral maturation. The results from this analysis will be used to computationally predict the effects of mutations at capsid subunit interfaces to be tested through experimental studies. In particular, we propose the following specific objectives: 1. Model the influence of charge interactions in Nudaurelia Omega (N¿V) and Bacteriophage HK97 virus maturation through pKa prediction and continuum electrostatic calculations. 2. Integrate our electrostatic modeling framework into a large-scale characterization of viral electrostatics in the VIPERdb to develop new features for viral structure analysis (http://viperdb.scripps.edu/) [1]. The proposed objectives build on existing experimental work in the Johnson lab on N¿v [2-11] and HK97 [12-25] as well as past research by McCammon, Baker, and others [26, 27] which used the NBCR-supported tools APBS (http://apbs.sf.net/) [28] and PDB2PQR (http://pdb2pqr.sf.net/) [29, 30] to explore capsid electrostatics in viral maturation. However, this collaborative project will significantly extend the scope of this work through the new finite element mesh generation technology [31] provided by the NBCR-supported tool FETK (http://www.fetk.org/) [32] and its integration with APBS.