Understanding biological glasses via large-scale molecular dynamics simulations

通过大规模分子动力学模拟了解生物玻璃

• 批准号: 2388766
• 金额: --
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2388766
• 关键词: Understanding; biological; glasses; via; large

Abstract(no more than 4,000 characters inc spaces) The glassy phase is a state of matter between a liquid and a solid. Glasses are like a liquid in the way that they are statistically isotropic, and they are like solids in that the atomic motion is largely suppressed. Considering the large plethora of glassy materials and the broad spectrum of routes that can lead to their formation, understanding the physical properties of glassy materials is one of the most difficult and, at the same time, fascinating "grand challenge problem" of our time [1]. Remarkably, Nature has found its way to preserve life during environmental stresses by taking advantage of glassy states. Anhydrobiosis (from the Greek "life without water") is an astounding strategy that allows certain spores, seeds, insects, crustaceans, nematodes, rotifers and tardigrades to survive environmental extremes such as, e.g., extreme drought, lack of nutrients, intense radiations, etc. During anhydrobiosis, these organisms increase the production of sugars (namely, threalose in invertebrates and sucrose in plants) up to a point in which sugars permeate inside and outside the cells replacing water molecules and creating a glassy matrix known as biological glass. The biological glass prevents otherwise lethal damages caused by the absence of water (like proteins and DNA unfolding, membranes rupture, etc.), and induces an almost completely desiccated state known as "tun" state, in which the metabolism of the organism either stops completely or decreases to a level that cannot be measured. On the other hand, when environmental circumstances eventually stabilize and water become available again, the biological glass melts and the metabolism increases, restoring all vital signs. This research will investigate the formation and the effects of biological glasses in a typical biophysical membrane via molecular dynamics simulations in order to understand (i) how biological glasses are formed in terms of dehydration rate, (ii) what are their properties depending on the adopted protocol, and (iii) how biological membranes recover functionality after rehydration. In order to achieve this goal, we will perform large-scale molecular dynamics simulations with the code GROMACS that can run on GPUs, as standard CPU simulations cannot tackle the complexity of this problem and the required long simulation times. We will simulate mixtures of water and sugar (trehalose or sucrose) confined in DMPC lipids. We will simultaneously model the behavior of the water+sugar+DMPC mixture at different concentrations of sugars (to mimic the sugar production in anhydrobiotes) and at different temperatures (to mimic desiccation conditions). For each system, we will perform dehydration-rehydration cycles. During the desiccation cycles, we will observe (as in experiments) the disruption of the DMPC membrane in the runs far from the ideal protocol adopted by anhydrobiotes, allowing us to identify and to characterize the mechanisms leading to and governing anhydrobiosis.From this project we will comprehensively draw a general picture of the thermodynamic conditions at which biological glasses are produced as well as the molecular mechanisms that lead to their formation, allowing us to understand how anhydrobiotes survive extreme conditions. [1] K. Binder and W. Kob. Glassy Materials and Disor- dered Solids. World Scientific, 2011. [2] S. Yashina, S. Gubin, S. Maksimovich, A. Yashina, E. Gakhova, and D. Gilichinskyb. Regeneration of whole fertile plants from 30,000-y-old fruit tissue buried in siberian permafrost. Proc. Natl. Ac. Sci. USA, 109:4008-4013, 2012.[3] D. Sloan, R. Alves Batista, and A. Loeb. The resilience of life to astrophysical events. Sci. Rep., 7:5419, 2017. [4] F. Martelli, H.-Y. Ko, E. C. Og uz, and R. Car. Local- order metric for condensed phase environments. Phys. Rev. B, 97:064105, 2016.

摘要（不超过4,000个字符，包括空格）玻璃相是介于液体和固体之间的物质状态。玻璃在统计上是各向同性的，就像液体一样，而它们在原子运动被大大抑制的情况下就像固体一样。考虑到大量的玻璃态材料和可能导致其形成的广泛途径，理解玻璃态材料的物理性质是我们这个时代最困难的，同时也是最吸引人的“大挑战问题”之一。值得注意的是，大自然已经找到了利用玻璃态在环境压力下保存生命的方法。脱水共生（来自希腊语“没有水的生命”）是一种惊人的策略，允许某些孢子、种子、昆虫、甲壳类动物、线虫、轮虫和缓步动物在极端环境中生存，例如，极端干旱、缺乏营养、强烈辐射等。在无水生物作用期间，这些生物体增加糖（即无脊椎动物中的threalose和植物中的蔗糖）的产量，直到糖渗透到细胞内外取代水分子并产生称为生物玻璃的玻璃状基质的程度。生物玻璃可防止因缺水而造成的其他致命损害（如蛋白质和DNA解折叠、膜破裂等），并诱导几乎完全干燥的状态，称为“tun”状态，其中生物体的新陈代谢完全停止或降低到无法测量的水平。另一方面，当环境条件最终稳定下来，水再次可用时，生物玻璃融化，新陈代谢增加，恢复所有生命体征。本研究将通过分子动力学模拟研究生物玻璃在典型生物物理膜中的形成和影响，以了解（i）生物玻璃如何在脱水速率方面形成，（ii）它们的特性取决于所采用的协议，以及（iii）生物膜如何在再水化后恢复功能。为了实现这一目标，我们将使用可以在GPU上运行的代码GROMACS进行大规模分子动力学模拟，因为标准的CPU模拟无法解决这个问题的复杂性和所需的长模拟时间。我们将模拟限制在DMPC脂质中的水和糖（海藻糖或蔗糖）的混合物。我们将同时模拟水+糖+DMPC混合物在不同糖浓度（模拟脱水生物中的糖生产）和不同温度（模拟干燥条件）下的行为。对于每个系统，我们将执行脱水-再水化循环。在干燥循环中，我们将观察到（如在实验中）在运行中DMPC膜的破坏远离脱水生物所采用的理想方案，使我们能够识别和表征导致和控制脱水生物作用的机制。从这个项目中，我们将全面描绘生物玻璃产生的热力学条件以及导致脱水生物作用的分子机制。它们的形成，让我们了解脱水生物如何在极端条件下生存。[1]K. Binder和W. Kob.玻璃质材料和无序固体。世界科学，2011年。[2]S. Yashina，S.古宾、S. Maksimovich，A. Yashina、E. Gakhova和D.吉利钦斯基b.从埋藏在西伯利亚冻土中的30，000年前的果实组织中再生出完整的可育植株。Proc. Natl. AC. Sci. USA，109：4008-4013，2012. [3]D.斯隆河Alves Batista和A.勒布生命对天体物理事件的适应力。Sci.代表：7：5419，2017. [4]F. Martelli，H. Y. Ko，E. C. Og uz，和R.车凝聚相环境的局部阶度规。Phys. Rev. B，97：064105，2016。