Collaborative Research: Geometrical Simulation of Biomolecular Mobility

研究人员调查生物分子（包括蛋白质和蛋白质复合物）的灵活性和流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，具有足够的刚性以维持其三维结构，但具有足够的柔性以发挥功能。换句话说，天然状态的蛋白质正好存在于从刚性到柔性的过渡阶段，在这个阶段，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。它们被设计成产生身体的运动学连接的真实运动，其服从长度和角度约束（共价键、锁定的肽双键和氢键），以及与各种原子类型相关的货车德瓦尔斯硬核半径，以及疏水性系链。该项目小组的联合专门知识将致力于确定新技术，用于高效、稳健和数学上严格的几何模拟，其灵感来自于真实的生物问题并应用于这些问题。研究人员对生物分子性质的研究汇集了数学，化学，工程，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性质方面的作用。不同学科概念的混合可能会产生新的见解，并阐明其他领域（除了生物学）中出现的问题，其中许多机构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。这种跨学科的方法对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。通过我们的工作正在开发的软件是免费提供给学术界通过Flexweb，这已经成为用户友好，并通过讨论论坛和每月网络会议推广。该软件在检测潜在生物危害的生物分子的研究中也应该是有用的。该项目部分在一所在科学界享有持久声誉的女子学院进行，有可能成为跨学科时代高素质研究和教育一体化的典范。

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.