Computer simulations of lipids

脂质的计算机模拟

• 批准号: RGPIN-2015-05305
• 负责人: Tieleman, Peter
• 金额: $ 6.48万
• 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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=692372
• 关键词: Computer; simulations; lipids

Biomolecules, such as proteins, DNA, lipids, and carbohydrates, exist in a microscopic universe with time and length scales 6-12 orders of magnitude smaller than the meters and seconds in which we measure length and time. They move rapidly on a time scale of nanoseconds and interact with individual water molecules the size of a few tenths of a nanometer. Most biomolecules are very small compared to the wavelength of visible light. This means they cannot be seen with ordinary microscopes, although there are many sophisticated experimental methods to measure aspects of the behaviour, shape, and interactions of biomolecules. Computer modeling is a complimentary approach to such experiments, both by themselves and in direct combination with experiments that otherwise could not be interpreted at a molecular level.***Using powerful computers and a description of how atoms interact with each other, it is possible to calculate in atomic detail how biomolecules move and interact in time. In recent years, this molecular dynamics simulation method has become an essential method to solve problems involving molecules of all types, in my research group primarily lipids. ***Lipids are the major building block of cell membranes that define the boundary between a cell and its surroundings. Cell membranes have remarkable mechanical and electrical properties, a complex chemical composition, and a surprisingly complex physical behaviour. These properties are primarily derived from the molecular structure of lipids, which have a water-loving head and a water-avoiding tail. This structure leads to self-aggregation in water into fascinating structures. These include cell membranes based on biological lipids, but also a wide variety of other structures by synthetic lipids and lipid mixtures, which are both of fundamental interest and of interest in technical and scientific applications. ***This research project is aimed at developing and applying computational models of molecules to better understand the properties of lipids and surfactant molecules. We will use and improve both detailed atomistic models and a somewhat coarser model in which a few atoms are grouped into a single 'bead'. Although we lose detail in this case, it is computational cheaper by several orders of magnitude to explore such models. Our main interests are the properties of domains in membranes, which are thought to underly many biologically important processes, the properties of mixtures of surfactants and lipids that form micelles, bicelles, and nanodiscs, and an improved link with experimental methods that give insight in lipid structure, including x-ray and neutron diffraction as well as spectroscopic methods. **

生物分子，如蛋白质、DNA、脂类和碳水化合物，存在于微观宇宙中，时间和长度尺度比我们测量长度和时间的米和秒小6-12个数量级。它们在纳秒的时间尺度上快速移动，并与只有十分之几纳米大小的单个水分子相互作用。与可见光的波长相比，大多数生物分子都非常小。这意味着它们不能用普通显微镜看到，尽管有许多复杂的实验方法来测量生物分子的行为、形状和相互作用的各个方面。计算机模拟是这类实验的一种补充方法，既可以单独进行，也可以直接与无法在分子水平上解释的实验相结合。*使用强大的计算机和对原子如何相互作用的描述，可以详细计算生物分子如何在时间上移动和相互作用。近年来，这种分子动力学模拟方法已经成为解决涉及所有类型分子的问题的基本方法，在我的研究组中主要是脂类。脂类是定义细胞与环境之间边界的细胞膜的主要构件。细胞膜具有显著的机械和电学性能，复杂的化学成分，以及令人惊讶的复杂的物理行为。这些特性主要来自于脂类的分子结构，它有一个亲水的头和一个避水的尾巴。这种结构导致在水中自我聚集成令人着迷的结构。其中包括基于生物脂类的细胞膜，也包括由合成脂类和脂类混合物构成的各种各样的其他结构，这既是基本的兴趣，也是技术和科学应用中的兴趣。本研究项目旨在开发和应用分子的计算模型，以更好地了解脂类和表面活性分子的性质。我们将使用和改进详细的原子论模型和稍微粗糙的模型，在该模型中，几个原子被组合成一个单一的“珠子”。尽管我们在这种情况下忽略了细节，但探索此类模型的计算成本要低几个数量级。我们的主要兴趣是膜中结构域的性质，这被认为是许多生物学上重要的过程，形成胶束、双胶束和纳米盘的表面活性剂和脂类混合物的性质，以及与实验方法的改进联系，这些方法提供了对脂质结构的洞察，包括X射线和中子衍射以及光谱方法。