Complementary Methods for Equilibrium Sampling of Biomolecules

智力优势：蛋白质和核酸经常像小型机器一样，在细胞中执行其他功能，如合成额外的分子，细胞内系统之间的通信/“信号”，以及运动。这种功能通常涉及分子形状的重大变化。目前的项目将开发用于研究这种分子运动的计算机模拟方法。新的方法将结合软件和硬件的进步。例如，正在开发新的软件，以利用在典型的当前模拟中未使用的99.9%的计算机内存。这类研究的重要性可以从生物分子时间尺度来理解：尽管当今特殊计算机上的尖端模拟可以达到微秒尺度，甚至对于小型系统来说可以达到微秒尺度，但人们普遍认识到，关键的生化现象发生在偶数秒或更长的时间尺度上--也就是说，比计算能力长100万倍。在这一计算鸿沟被弥合之前，要系统地研究维持细胞工作的各种生物分子运动将是极其困难的。除了研究之外，该提案还从两个方面针对科学教育学。首先，首席研究员将准备他的教科书《生物分子统计物理学：导论》的第二版，内容大大扩充。这本书是为现代跨学科研究生(例如，生物物理学或计算生物学)写的，他们来自不同的半定量背景。它解释了生物分子行为背后的物理原理。其次，首席研究员将针对现代科学教育中的一个重大缺陷：科学写作。将开发一门新的课程和辅助网络材料，面向浸泡在“新媒体”中的现代学生。当今世界的复杂性要求科学写作既要有信息量，又要有吸引力。

Intellectual merit:Proteins and nucleic acids often act like small machines, carrying out functions in the cell such as the synthesis of additional molecules, communication/'signaling' among systems in the cell, and locomotion. Such functions typically involve significant changes to the shapes of the molecules. Computer simulation methodology for studying such molecular motions will be developed in the current project. The new methodology will combine advances in software and hardware. For example, new software is being developed to exploit the 99.9% of computer memory that goes unused in typical current simulations. The importance of this type of research can be understood in terms of biomolecular timescales: although cutting-edge simulations on special computers today can reach the microsecond scale or even beyond for small systems, it is widely appreciated that key biochemical phenomena occur at timescales of even seconds and longer - that is, one million times longer than computational capacity. Until this computing gap is bridged, it will be extremely difficult to systematically study the full range of biomolecular motions which keep cells working.Broader impactsBesides research, the proposal targets science pedagogy in two ways. First, the principal investigator will prepare a significantly expanded second edition of his textbook, Statistical Physics of Biomolecules: An Introduction. This book is written for modern interdisciplinary graduate students (e.g., in biophysics or computational biology) who come from diverse semi-quantitative backgrounds. It explains the physical principles underlying biomolecular behavior. Second, the principal investigator will target a significant deficiency in modern science education: science writing. A new course and auxiliary web materials will be developed, geared toward modern students saturated with "new media". The complexities of today's world demand that science writing should be both informative and appealing.