Functional Dynamics of the Myosin Molecular Motor

肌球蛋白分子马达的功能动力学

• 批准号: 7216844
• 负责人: YURI NESMELOV
• 金额: $ 10.87万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7216844
• 关键词: ATP phosphohydrolase; Actins; Actomyosin; Actomyosin Adenosinetriphosphatase; Address; Binding; Binding Sites; Biochemical; Biological; Biomedical Research; Biophysics; Computing Methodologies; Coupled; DNA Sequence Rearrangement; Data; Data Analyses; Development; Development Plans; Dictyostelium; Electromagnetic Fields; Electron Spin Resonance Spectroscopy; Elements; Equilibrium; Event; Fluorescence; Funding; Generations; Goals; Helix (Snails); Hydrolysis; Journals; Kinetics; Label; Learning; Measurement; Mechanics; Mentors; Methods; Minnesota; Molecular; Molecular Biology; Molecular Conformation; Molecular Genetics; Molecular Motors; Molecular and Cellular Biology; Motion; Motor; Muscle; Muscle Proteins; Muscle function; Muscular Dystrophies; Myosin ATPase; Nucleotides; P(3)-1-(2-nitro)phenylethyladenosine 5' -triphosphate; Personal Satisfaction; Phase; Physics; Positioning Attribute; Preparation; Proteins; Pyrenes; Research; Research Personnel; Resources; Rotation; Sampling; Scientist; Signal Transduction; Site; Solutions; Specialist; Spin Labels; Structural Protein; Structure; Techniques; Time; Training; Training Programs; Universities; Work; aqueous; base; career; chemical kinetics; design; ear helix; insight; interdisciplinary approach; molecular dynamics; mutant; nucleotide analog; photolysis; protein structure; pyrene; quantum; research and development; research study

DESCRIPTION (provided by applicant): The applicant, Dr. Yuri E. Nesmelov, is a physicist whose research has focused on the interaction of electromagnetic fields with matter. Dr. Nesmelov proposes to learn and utilize molecular biophysical and biochemical techniques to round out a multidisciplinary approach to be used in studying myosin functional dynamics. Career Development/Training Plan: The primary element of the plan will be the acquisition of advanced molecular biophysical and biochemical techniques from mentored training. The majority of the training will come from the primary mentor, Dr. David D. Thomas, who is an internationally known scientist in the field of muscle biophysics, and is the director of an NIH-funded training program in muscle research. Additional training in cell and molecular biology will be provided by the co-mentor, Dr. Margaret Titus, who is well known for her work on myosin. Part of the research (W band electron paramagnetic resonance (EPR)) will be performed with a collaborator, Dr. Peter Fajer, a renowned specialist in biological EPR and muscle biophysics. Structured activities for further career and research development will include attendance and participation at national scientific meetings, regular involvement in journal clubs and seminars, and affiliation with the Muscular Dystrophy Center at the University of Minnesota. Research Plan: The overall aim of this proposal is for Dr. Nesmelov to learn molecular biophysical and biochemical techniques and apply them together with site-directed spin labeling and multifrequency EPR spectroscopy, to explore internal dynamics of myosin motor functioning. The proposed work is based on recent developments by the applicant in sensitivity improvement for EPR measurement, especially for experiments on myosin in solution, and in multifrequency EPR data analysis, to accurately characterize the dynamics of a proteinbound spin label. This approach will be used to obtain detailed information about the dynamic rearrangement of protein structural elements. These methods will be developed further, and used to define the kinetics of structural rearrangements of the relay helix and SH1 helix in myosin during the actomyosin ATPase cycle.

描述（由申请人提供）：申请人Yuri E. Nesmelov博士是一位物理学家，其研究重点是电磁场与物质的相互作用。 Nesmelov博士建议学习和利用分子生物物理和生化技术，以完善一种用于研究肌球蛋白功能动力学的多学科方法。职业发展/培训计划：该计划的主要要素是从指导培训中获取先进的分子生物物理和生化技术。大多数培训将来自主要导师David D. Thomas博士，他是肌肉生物物理学领域的国际知名科学家，并且是NIH资助的肌肉研究培训计划的主任。同事玛格丽特·泰特斯（Margaret Titus）博士将提供细胞和分子生物学的其他培训，后者以肌球蛋白的工作而闻名。研究的一部分（W带电子顺磁共振（EPR））将与合作者Peter Fajer博士（生物EPR和肌肉生物物理学专家）一起进行。进一步职业和研究发展的结构化活动将包括参加国家科学会议，定期参与期刊俱乐部和研讨会以及与明尼苏达大学肌肉营养不良中心的隶属关系。研究计划：该提案的总体目的是让Nesmelov博士学习分子生物物理和生化技术，并将它们与位置定向的自旋标记和多频EPR光谱一起应用，以探索肌球蛋白运动功能的内部动力学。拟议的工作基于申请人在EPR测量方面的敏感性提高方面的最新发展，尤其是用于溶液中肌球蛋白的实验以及多频EPR数据分析，以准确表征蛋白质旋转标记的动力学。该方法将用于获取有关蛋白质结构元素动态重排的详细信息。这些方法将进一步开发，并用于定义肌动蛋白ATPase循环期间肌球蛋白中继电器螺旋和SH1螺旋的结构重排的动力学。