Analysis of Moving Unfolding Fronts in Long Protein Molecules

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拉伸的蛋白质的非平衡机械化学行为。这种方法的关键新奇是使用连续波动杆模型（和盟军的计算方法）与异质性的机械性能的表示部分未折叠的蛋白质，而不是完全原子的生物分子的描述。研究分为三个项目：（a）将球状蛋白质寡聚体建模为非均质波动杆，并使用基于高斯积分的计算技术确定其在不同加载条件下的响应，（B）将卷曲螺旋蛋白质建模为具有多阱自由能的1D连续体，并使用相变理论预测其力-延伸响应，（c）利用具有朗之万动力学的珠-弹簧模型，了解棒状分子（如卷曲螺旋）中展开前沿的传播动力学，如果这项工作成功，将对揭示与疾病发病机制（如肌肉萎缩症、过早衰老）有关的卷曲螺旋蛋白的机械行为产生重大影响，中风、心脏病和伤口愈合它还将有助于理解蛋白质和DNA在治疗剂制造的工业过程中遇到的大流体施加剪切下的反应。该教育计划将通过教授题为生物力学中的熵力的新研究生课程和指导本科生做短期暑期项目，在纳米技术和生物物理学的高度跨学科领域向研究生和本科生提供培训。外联计划包括：（a）与当地一家新成立的公司合作，开展与绘制人类基因组有关的项目;（B）在国际会议上组织专题讨论会和高级学校;（c）开展针对少数民族高中学生和教师的活动。

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.