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，博士尤里E。Nesmelov是一位物理学家，他的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物化学技术，以完善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：该计划的主要内容将是通过指导培训获得先进的分子生物物理和生物化学技术。大部分培训将来自主要导师，大卫D博士。托马斯是肌肉生物物理学领域的国际知名科学家，也是NIH资助的肌肉研究培训项目的负责人。细胞和分子生物学方面的额外培训将由共同导师Margaret Titus博士提供，她以肌球蛋白方面的工作而闻名。部分研究（W波段电子顺磁共振（EPR））将与合作者Peter Fajer博士一起进行，他是生物EPR和肌肉生物物理学方面的著名专家。进一步的职业和研究发展的结构化活动将包括出席和参加国家科学会议，定期参加期刊俱乐部和研讨会，并与明尼苏达大学的肌肉营养不良中心联系。研究计划：Nesmelov博士学习分子生物物理和生物化学技术，并将其与定点自旋标记和多频EPR光谱一起应用，以探索肌球蛋白运动功能的内部动力学。拟议的工作是基于最近的发展，由申请人在EPR测量的灵敏度提高，特别是在溶液中的肌球蛋白的实验，并在多频EPR数据分析，以准确地表征动态的蛋白质自旋标签。这种方法将被用来获得有关蛋白质结构元素的动态重排的详细信息。这些方法将进一步发展，并用于定义在肌动球蛋白ATP酶循环过程中肌球蛋白中的中继螺旋和SH 1螺旋的结构重排的动力学。