Probing the molecular structure of water at the interface with the HGB and RG-II polysaccharide

探测水与 HGB 和 RG-II 多糖界面处的分子结构

• 批准号: 2107310
• 金额: --
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2107310
• 关键词: Probing; molecular; structure; water; interface

1. Aims and ObjectivesWe aim to probe the molecular structure of water at the interface with the polysaccharides RG-II (found within pectin) and homogalacturonan, HGB, (which forms the backbone of RG-II) both at room tem- perature and supercooling. We hope this work will shed light on whether these polysaccharides have the functionality to either inhibit or promote the formation of ice. Tentative results from our experimental collaborators at the University of Durham and Leeds have already marked RG-II to be a potential Ice Recrystallisation Inhibitor. One of the key questions we wish to address is what structural features need to be available for these molecules to bind with ice. At present there is much debate surrounding the ice-binding mechanisms of predominantly ice-binding proteins and glycoproteins [1, 2]. Various studies have found different mechanisms which can range from direct hydrogen bonding of a molecule to a growing ice crystal, to indirect binding via the arrangement of clathrate waters which fuse to the ice crystal interface [3, 4, 5].2. MethodologyThis is a computational project, in collaboration with experimentalists both at the University of War- wick as well as Durham and Leeds. We are using classical molecular dynamics (MD) to simulate the polysaccharides, in conjunction with enhanced sampling methods such a metadynamics based on free-energy calculations [6]. 3. ContextUnderstanding the formation of ice in biological matter is key to furthering cryopreservation technologies. Preventing ice recrystallisation over increasing freezing resistance is particularly preferable in cryopreservation techniques, as most damage arises during the thawing stages of the biomolecules where the small ice crystals in the extracellular matrix are most susceptible to recrystallisation [7]. In our work we will look at the possibility of polysaccharides acting as potential IRIs. There is good reason for this, these molecules have not been as widely studied as their protein counterparts. Polysaccharides tend to be more resistant to degradation and denaturation, cheaper to produce as well as being smaller. We anticipate that our work will add further insights to the cryopreservation techniques which in turn are essential to deliver the next generation of medical treatments such a regenerative and translational medicine.

1.目的和目的我们的目的是探测在室温和过冷下，水与多糖RG-II（存在于果胶中）和同型半乳糖醛酸（HGB）（其形成RG-II的主链）的界面处的分子结构。我们希望这项工作将揭示这些多糖是否具有抑制或促进冰形成的功能。我们在达勒姆大学和利兹大学的实验合作者的初步结果已经标志着RG-II是一种潜在的冰重结晶抑制剂。我们希望解决的一个关键问题是，这些分子需要什么样的结构特征才能与冰结合。目前，围绕主要是冰结合蛋白和糖蛋白的冰结合机制有很多争论[1，2]。各种研究已经发现了不同的机制，其范围可以从分子与生长的冰晶的直接氢键结合，到通过融合到冰晶界面的笼形沃茨的排列的间接结合[3，4，5]。方法这是一个计算项目，与实验学家都在大学的沃威克以及达勒姆和利兹合作。我们正在使用经典分子动力学（MD）来模拟多糖，结合增强的采样方法，例如基于自由能计算的metadaptics [6]。3.了解生物物质中冰的形成是进一步发展低温保存技术的关键。在冷冻保存技术中，防止冰重结晶超过增加抗冻性是特别优选的，因为大多数损伤在生物分子的解冻阶段出现，其中细胞外基质中的小冰晶最容易重结晶[7]。在我们的工作中，我们将研究多糖作为潜在IRI的可能性。这是有充分理由的，这些分子没有像它们的蛋白质对应物那样被广泛研究。多糖往往更能抵抗降解和变性，生产成本更低，体积更小。我们预计，我们的工作将为冷冻保存技术提供进一步的见解，而冷冻保存技术对于提供下一代医学治疗（如再生和转化医学）至关重要。