Development of integrative approaches to biomolecular structure determination

生物分子结构测定综合方法的发展

基本信息

批准号：
RGPIN-2015-03730
负责人：
MacCallum, Justin
金额：
$ 1.82万
依托单位：
University of Calgary
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2018
资助国家：
加拿大
起止时间：
2018-01-01 至 2019-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=658211
关键词：
Development integrative approaches biomolecular structure

项目摘要

The aim of this Discovery research program is to develop new ways to determine the structure of biomolecules by combining emerging experimental techniques with tools from physical chemistry, namely statistical mechanics and molecular simulation. ***Proteins are life's little machines. These tiny molecules are responsible for replicating our DNA, turning food into energy, contracting our muscles, and conducting electrical signals in our nervous systems-among many other activities. The function of each protein depends on its structure: the specific three-dimensional shape that each protein folds into. We now know over 100,000 different protein structures, which are curated in the Protein Data Bank. These structures have helped to reveal the extraordinary story of how life functions at the molecular level. This story, however, is incomplete because there are many proteins and protein complexes (groups of proteins that stick together and form larger structures) that we still do not know. This is because not all proteins or complexes are amenable to the experimental techniques that structural biologists routinely use.***This research program is focused on developing new ways to determine protein structures that combine experiments with sophisticated computational tools built upon the foundation of statistical mechanics. Our focus is on a range of emerging experimental techniques that produce sparse, ambiguous, or noisy data. There are many experiments that fall into this category, some of which have been around for decades. These experiments have not been widely used in structural biology in the past because the data they produce is difficult to interpret. My lab is working to combine these experiments with sophisticated computational tools that can overcome the challenges in interpretation, which will unlock new avenues for the determination of protein structure.***Over the five year span of this Discovery Grant, my laboratory's objectives are to further develop combinations of experiment and computation that can solve current challenges in structural biology. My lab aims to establish proofs-of-principal that demonstrate the success and effectiveness of these methods on a variety of model systems. The long-term goal of this project is to enable a range of new approaches to structural biology that will allow us to reveal protein structures that are currently hidden. By providing structural biologists with new tools, we will contribute to a better understanding of how life functions at the molecular level.**

该发现研究计划的目的是通过将新兴实验技术与物理化学工具（即统计力学和分子模拟）相结合，开发确定生物分子结构的新方法***蛋白质是生命的小机器。复制我们的 DNA、将食物转化为能量、收缩我们的肌肉以及在我们的神经系统中传导电信号等许多其他活动。每种蛋白质的功能取决于其结构：每种蛋白质折叠成的特定三维形状。我们现在知道了蛋白质数据库中收录了 100,000 种不同的蛋白质结构，这些结构有助于揭示生命如何在分子水平上发挥作用的非凡故事。然而，这个故事是不完整的，因为存在许多蛋白质和蛋白质复合物。粘在一起并形成更大结构的蛋白质），这是我们仍然不知道的，这是因为并非所有蛋白质或复合物都适合结构生物学家使用的实验技术。***该研究计划的重点是开发确定蛋白质的新方法。将实验与复杂的结构相结合我们的重点是一系列产生稀疏、模糊或噪声数据的新兴实验技术，其中一些实验已经存在了几十年。过去，实验并未在结构生物学中得到广泛应用，因为它们产生的数据难以解释，我的实验室正在努力将这些实验与复杂的计算工具结合起来，以克服解释方面的挑战，这将为确定结果开辟新的途径。蛋白质结构。***五年来在这项发现资助的范围内，我的实验室的目标是开发进一步的实验和计算组合，以解决结构生物学当前的挑战。我的实验室的目标是建立原理证明，证明这些方法在各种方面的成功和有效性。该项目的长期目标是实现一系列新的结构生物学方法，使我们能够揭示目前隐藏的蛋白质结构。通过为结构生物学家提供新工具，我们将有助于更好地理解。生命如何在分子层面发挥作用等级。**