Analysis of Moving Unfolding Fronts in Long Protein Molecules

长蛋白质分子中移动展开前沿的分析

• 批准号: 1066787
• 负责人: Prashant Purohit
• 金额: $ 29.98万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-10-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1066787&HistoricalAwards=false
• 关键词: Analysis; Moving; Unfolding; Fronts; Long

The research objective of this award is to determine the non-equilibrium mechano-chemical behavior of proteins stretched in atomic force microscopes and microfluidic devices. The key novelty of this approach is the use of continuum fluctuating rod models (and allied computational methods) with heterogeneous mechanical properties as representations of partially unfolded proteins rather than fully atomistic descriptions of the biomolecules. The research is divided into three projects: (a) model a globular protein oligomer as a heterogeneous fluctuating rod and determine its response under different loading conditions using a computational technique based on Gaussian integrals, (b) model a coiled-coil protein as a 1D continuum with a multi-well free energy and predict its force-extension response using a theory of phase transitions, (c) understand the kinetics of propagating unfolding fronts in rod-like molecules, such as coiled-coils, using a bead-and-spring model with Langevin dynamics.If successful this work will have a major impact in unraveling the mechanical behavior of coiled-coil proteins central to the pathogenesis of diseases, such as, muscular dystrophy, premature ageing, stroke, heart disease and wound healing. It will also help understand the response of proteins and DNA under large fluid imposed shears which are encountered in industrial processes in the manufacture of therapeutics. The education plan will impart training to graduate and undergraduate students in the highly interdisciplinary areas of nanotechnology and biophysics by teaching a new graduate course titled Entropic forces in biomechanics and mentoring undergraduates to do short summer projects. The outreach plan includes (a) working with a local start-up company on projects related to mapping the human genome, (b) organizing symposia and advanced schools in international conferences, and (c) activities targeted at minority students and teachers in high schools.

该奖项的研究目标是确定在原子力显微镜和微流体设备中伸展的蛋白质的非平衡机械化学行为。这种方法的主要新颖性是使用具有异质机械性能的连续性波动模型（以及相关计算方法）作为部分展开的蛋白质的表示，而不是对生物分子的完全原子描述。该研究分为三个项目：（a）模拟球状蛋白寡聚作为异质波动杆的模型，并使用基于高斯积分的计算技术在不同的负载条件下确定其响应具有多孔自由能的连续体，并使用相变理论来预测其力扩展响应，（c）了解使用珠和螺旋形分子（例如盘绕的螺旋）在传播前线的动力学，例如使用珠子和螺旋线。如果成功的春季模型，这项工作将对揭示对疾病发病机理的中心的机械行为产生重大影响，例如，肌肉营养不良，早衰，中风，心脏病，心脏病和伤口愈合。它还将有助于了解蛋白质和DNA在大型液体施加的剪切物下的反应，这些剪切物在工业过程中遇到的治疗疗法中遇到。该教育计划将通过在纳米技术和生物物理学的高度跨学科领域的毕业生和本科生进行培训，通过教授新的研究生课程，名为“生物力学和指导本科生”的新研究生课程，以做短暂的夏季项目。外展计划包括（a）与当地的一家初创公司合作，从事与人类基因组绘制的项目，（b）在国际会议上组织研讨会和高级学校，以及（c）针对高中少数学生和老师的活动。