Measurements of Protein Dynamics to Elucidate Protein and Enzyme Function.

蛋白质是执行活细胞大部分工作的分子机器。例如，它们负责合成和修复构成细胞的几乎所有分子。蛋白质通过改变其形状来响应与其他分子的相互作用，从而实现其生物活性。这一点早已为人所知，但蛋白质如何改变形状的详细机制一直难以确定。这是因为测量细节需要在十亿分之一秒和百万分之一秒的时间尺度上跟踪蛋白质中每个原子的位置。这一研究领域被称为“蛋白质动力学”，它有望揭示对蛋白质功能机制的最深刻理解。在我的NSERC发现计划的下一个5年周期中，我和我的学生将应用核磁共振波谱、质谱、氢交换化学、x射线衍射和分子动力学模拟等技术，在大范围的时间尺度上测量三种蛋白质的动力学，以便将原子动力学与每种蛋白质的紧急生物活性联系起来。蛋白质动力学领域的进展将对我们对生命的理解产生深远的影响，并将在生物技术、工业催化和药物设计方面有实际应用。该研究将由研究生和本科生进行，他们将接受最先进的蛋白质动力学理论和实践方法的培训。

Proteins are molecular machines that carry out most of the work of a living cell. For example, they are responsible for synthesizing and repairing nearly all of the molecules that make up a cell. Proteins carry out their biological activities by changing their shapes in response to interactions with other molecules. This has been known for a long time but the detailed mechanisms of how proteins change their shapes have been difficult to determine. That’s because measuring the details requires tracking the position of each atom in a protein on a timescale of billionths and millionths of a second. This field of study is called “protein dynamics” and it promises to reveal the deepest understanding of the mechanisms by which proteins function. Over the next 5 year cycle of my NSERC Discovery program, my students and I will apply the techniques of NMR spectroscopy, mass spectrometry, hydrogen exchange chemistry, X-ray diffraction and molecular dynamics simulations to measure the dynamics of three proteins over a wide range of timescales in order to connect the atomic dynamics to the emergent biological activity of each of the proteins. Advances in the field of protein dynamics will have a profound effect on our understanding of life and will have practical applications in biotechnology, industrial catalysis and drug design. The research will be conducted by graduate and undergraduate students who will be trained in the most advanced methods in the theory and practice of protein dynamics.