Collaborative Research: Geometrical Simulation of Biomolecular Mobility

合作研究：生物分子运动的几何模拟

• 批准号: 0714934
• 负责人: Ileana Streinu
• 金额: $ 33.01万
• 依托单位: Smith College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0714934&HistoricalAwards=false
• 关键词: Collaborative; Research; Geometrical; Simulation; Biomolecular

The investigators investigate mathematical and algorithmic problems arising in studies of the flexibility and mobility of biomolecules, which include proteins and protein complexes. Many proteins exist in their native state with enough rigidity to maintain their three dimensional structure, but with sufficient flexibility to function. In other words, native state proteins exist right at the transition from rigid to flexible, where small stimuli can produce large functional responses. To study this behavior, the investigators propose a new category of constrained simulations, called geometric simulations since they enforce equality and inequality constraints of a geometric nature. They are designed to produce realistic motions of kinematic linkages of bodies, which obey length and angle constraints (covalent bonds, locked peptide double bonds and hydrogen bonds), and van der Waals hard core radii associated with various atom types, as well as hydrophobic tethers. The project team's joint expertise will be devoted to identify new techniques for efficient, robust and mathematically rigorous geometric simulations, inspired by and applied to real biological problems. The investigators' study of the properties of biomolecules brings together concepts from mathematics, chemistry, engineering, computer science and physics to unify the various manifestations of structural flexibility, and to better understand their roles in determining observable properties. This mixing of concepts from different disciplines is likely to produce new insights, and shed light on problems arising in other areas (besides biology) where many bodies are interconnected by linkages and exclusion zones, as in material science, cell dynamics and crowd motion. This kind of interdisciplinary approach is particularly valuable to graduate and advanced undergraduate students, who can see unexpected connections between seemingly disparate areas of science. The software that is being developed through our work is freely available to the academic community via Flexweb, which has been made user-friendly and is promoted through discussion forums and monthly net-meetings. This software should also be useful in research involved in detecting biomolecules that are potential biohazards. This project, conducted in part at an all-women college with a sustained reputation in the sciences, has the potential for becoming a model of integration of high-caliber research and education in an era of interdisciplinarity.

研究人员研究了生物分子（包括蛋白质和蛋白质复合物）的灵活性和移动性研究中出现的数学和算法问题。许多蛋白质以其天然状态存在，具有足够的刚性来维持其三维结构，但具有足够的灵活性来发挥作用。换句话说，天然状态蛋白质存在于从刚性到柔性的过渡阶段，此时小的刺激可以产生大的功能反应。为了研究这种行为，研究人员提出了一种新的约束模拟类别，称为几何模拟，因为它们强制执行几何性质的等式和不等式约束。它们旨在产生物体运动连接的真实运动，这些运动遵循长度和角度约束（共价键、锁定肽双键和氢键）、与各种原子类型相关的范德华硬核半径以及疏水系链。该项目团队的联合专业知识将致力于确定高效、稳健和数学上严格的几何模拟的新技术，这些模拟受到真实生物问题的启发并应用于实际生物问题。研究人员对生物分子特性的研究汇集了数学、化学、工程学、计算机科学和物理学的概念，以统一结构灵活性的各种表现形式，并更好地理解它们在确定可观察特性中的作用。这种来自不同学科的概念的混合可能会产生新的见解，并揭示其他领域（生物学除外）中出现的问题，在这些领域中，许多物体通过联系和禁区相互连接，如材料科学、细胞动力学和群体运动。这种跨学科方法对于研究生和高年级本科生特别有价值，他们可以看到看似不同的科学领域之间意想不到的联系。我们正在开发的软件可以通过 Flexweb 免费提供给学术界，该软件已经变得用户友好，并通过讨论论坛和每月的网络会议进行推广。该软件在涉及检测潜在生物危害的生物分子的研究中也应该有用。该项目部分在一所在科学界享有盛誉的女子学院进行，有潜力成为跨学科时代高水平研究和教育一体化的典范。