MD and MC Studies of Hu and IHF Complexes with Unusual Forms of DNA

Hu 和 IHF 与异常 DNA 形式的复合物的 MD 和 MC 研究

基本信息

批准号：
8011323
负责人：
Susan Nicole Pieniazek
金额：
$ 3.23万
依托单位：
WESLEYAN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-01-15 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8011323
关键词：
Area Binding Binding Sites Biochemistry Bioinformatics Biological Process Biophysics Chemical Structure Chemicals Chemistry Complex Computational Technique Computer Simulation Computing Methodologies Cruciform DNA DNA DNA Structure DNA-Binding Proteins Data Development Disease Distal Doctor of Philosophy Elements Entropy Equilibrium Exhibits Family Fellowship Fluorescence Resonance Energy Transfer Free Energy Gene Expression Genetic Recombination Goals Health Heating Histones Indium Integration Host Factors Ions Knowledge Learning Measurement Mentors Methods Modeling Molecular Molecular Biology Molecular Conformation Molecular Models Names Nature Nucleic Acids Oligonucleotides Organic Chemistry Play Process Protein Binding Protein Dynamics Proteins Protocols documentation RNA-Binding Proteins Raman Spectrum Analysis Replication Initiation Reporting Research Role Series Site Sodium Chloride Solvents Structure System Techniques Thermodynamics Training Transcriptional Regulation Universities Update Ursidae Family Water base dimer enthalpy experience fighting flexibility functional group interest models and simulation molecular dynamics molecular mechanics molecular modeling molecular recognition nanosecond planetary Atmosphere professor programs protein structure quantum research study role model simulation single molecule skills success supercomputer theories ultraviolet

项目摘要

DESCRIPTION (provided by applicant): The objective of the proposed fellowship research is to elucidate the complex formation of the eubacterial proteins HU and IMF to unusual forms of DNA using the theory and methodologies of computational biophysics. Specific systems to be considered involve the proteins binding to highly bent forms of the DNA double helix that play a role in transcriptional regulation, site specific recombination and the initiation of replication, and to the four-way Holliday junction formed when DNA undergoes genetic recombination. The specific methods to be used are computationally intensive molecular dynamics and Monte Carlo simulations which require supercomputer facilities. The proteins, DNA, solvent water, and experimental salt conditions will be treated with a discrete all-atom model in the calculation of energies and forces. HU- and IHF-DNA complex formation at a high level of computational rigor and, in the process, enables the analysis of the free energy of binding in terms of the chemical forces acting at critical junctures. The new knowledge obtained in this research will provide a basis for the interpretation of experimental results and an understanding of the mechanisms of action in these biological processes at the sub-molecular level. PUBLIC HEALTH RELEVANCE: Special proteins activate DNA and facilitate gene expression. The goal of this proposal is to use modern computational techniques to learn how these proteins interact with DNA. Understanding the control over these interactions is critical in the development of agents used to fight disease.

描述（由申请人提供）：拟议的奖学金研究的目的是利用计算生物物理学的理论和方法阐明真细菌蛋白 HU 和 IMF 与不寻常 DNA 形式的复杂形成。需要考虑的特定系统涉及与高度弯曲形式的 DNA 双螺旋结合的蛋白质，这些双螺旋在转录调节、位点特异性重组和复制启动中发挥作用，以及与 DNA 进行基因重组时形成的四路霍利迪连接体结合。具体使用的方法是计算密集型分子动力学和蒙特卡罗模拟，需要超级计算机设施。在计算能量和力时，将使用离散全原子模型处理蛋白质、DNA、溶剂水和实验盐条件。 HU-和IHF-DNA 复杂的形成在高水平的计算严谨性下进行，在此过程中，能够根据作用在关键时刻的化学力来分析结合自由能。这项研究中获得的新知识将为解释实验结果和在亚分子水平上理解这些生物过程的作用机制提供基础。公共卫生相关性：特殊蛋白质可激活 DNA 并促进基因表达。该提案的目标是利用现代计算技术来了解这些蛋白质如何与 DNA 相互作用。了解对这些相互作用的控制对于开发用于对抗疾病的药物至关重要。