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.

研究人员研究了包括蛋白质和蛋白质复合物在内的生物分子的柔韧性和迁移性研究中引起的数学和算法问题。许多蛋白质存在于其本地状态，具有足够的刚性以保持其三维结构，但具有足够的灵活性。换句话说，天然状态蛋白在从刚性到柔性的过渡中存在，小刺激可以产生大量的功能反应。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，因为它们会实施平等和不平等的几何性质。它们的设计目的是产生身体的运动连接的现实动作，这些运动遵循长度和角度约束（共价键，锁定的肽双键和氢键）以及与各种原子类型相关的范德华硬核半径以及疏水性恐怖量。项目团队的共同专业知识将致力于确定新技术，以实现高效，健壮和数学上严格的几何模拟，并受到实际生物学问题的启发并应用。研究人员对生物分子特性的研究将数学，化学，工程，计算机科学和物理学的概念汇总在一起，以统一结构灵活性的各种表现，并更好地了解它们在确定可观察性质中的作用。来自不同学科的概念的这种混合可能会产生新的见解，并阐明了在其他领域（除生物学外）出现的问题，在这些领域（除了生物学外），许多身体都与链接和排除区相互联系，就像材料科学，细胞动力学和人群运动一样。这种跨学科的方法对于毕业和高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外的联系。通过我们的工作开发的软件可以通过FlexWeb自由使用，该软件已被用户友好，并通过讨论论坛和每月的网络会促进。该软件还应用于检测潜在生物危害的生物分子的研究。该项目部分在一所全妇女学院进行，在科学中持续声誉，有可能成为跨学科时代的高素质研究和教育融合的模型。