Free Energies in Biomolecular Systems: Development and Applications of Theoretical and Computational Approaches

生物分子系统中的自由能：理论和计算方法的发展和应用

• 批准号: 0920261
• 负责人: Benoit Roux
• 金额: $ 68.81万
• 依托单位: University of Chicago
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0920261&HistoricalAwards=false
• 关键词: Free; Energies; Biomolecular; Systems; Development

Biology, at the atomic level, is fundamentally controlled by the activity and interactions of a wide range of different molecules. Some, such as proteins and nucleic acids, are large and highly complex chemical structures called macromolecules. Others are small chemical compounds, which can be as simple as a single water molecule. One of the most basic questions about any of the molecules in the living cell is the manner by which they interact and associate with one another. How molecules recognize and bind to a specific partner plays a key role in biology. For example, this is one of the ways biological "signals" and information are transmitted and communicated within and between living cells, and how specific processes are triggered and synchronized. The research project consists in improving the theoretical and computational methods to calculate and predict accurately how molecules bind to one another. According to the theory of statistical thermodynamics, the quantity that controls the association of molecules is the "binding free energy". This mathematically well-defined quantity can be calculated using computer simulations of atomic models of the molecules of interest. One method, which is called "molecular dynamics" simulation, can help elucidate the fundamental principles governing the binding of biological molecules at the atomic level. Efforts in this area have great intellectual merit because biology is entering a quantitative era that requires an ability to predict the binding of molecules.This research is carried out in an academic environment and one essential aspect to the broader impact is the education and training of highly qualified personnel. The students and postdoctoral researchers involved in the research project will ultimately join the job market, either in academia or in industry, and their advanced skills will contribute to the vitality of society. Furthermore, improving the ability to predict binding accurately using computations has great pragmatic value and is expected to have a broad impact on a vast array of fundamental problems in biology and chemistry. For example, technological advances in this area could be used to engineer and design better method to detect, capture, and extract toxic molecules from the environment (bioremediation). Lastly, all the new knowledge produced by the research in the form of theories, explanation, and computer programs is freely disseminated via the PI's lab web site for the benefit of the entire community.

在原子水平上的生物学从根本上受到各种不同分子的活性和相互作用的控制。有些，例如蛋白质和核酸，是称为大分子的大型且高度复杂的化学结构。其他是小型化合物，可以像单个水分子一样简单。关于活细胞中任何分子的最基本问题之一是它们相互作用并相互关联的方式。分子如何识别并与特定伴侣结合在生物学中起关键作用。例如，这是生物学“信号”和信息之间和在活细胞之间传输和传达信息的方式之一，以及如何触发和同步特定过程。研究项目包括改进理论和计算方法，以准确计算和预测分子如何相互结合。根据统计热力学理论，控制分子缔合的数量是“结合自由能”。该数学定义明确的数量可以使用感兴趣分子的原子模型进行计算机模拟来计算。一种称为“分子动力学”模拟的方法可以帮助阐明控制原子水平生物分子结合的基本原理。这一领域的努力具有很大的智力优点，因为生物学进入了一个定量时代，需要预测分子的结合能力。这项研究是在学术环境中进行的，对更广泛影响的一个基本方面是对高素质人员的教育和培训。参与研究项目的学生和博士后研究人员最终将加入就业市场，无论是学术界还是行业，他们的高级技能将有助于社会的活力。此外，提高使用计算准确预测结合的能力具有很高的务实价值，并且预计将对生物学和化学中的各种基本问题产生广泛的影响。例如，该领域的技术进步可用于设计和设计更好的方法来检测，捕获和从环境中提取有毒分子（生物修复）。最后，研究以理论，解释和计算机程序形式产生的所有新知识都通过PI的实验室网站自由传播，以使整个社区受益。