Combining Molecular Dynamics and Neutron Reflectometry Techniques to Understand Lipid Transfer Protein Binding Events at the Membrane Interface

植物脂质转运蛋白（plant lipid transfer proteins，PLTPs）具有结合和转运脂质的能力，被认为是植物在陆地生存的关键蛋白。PLTPs在植物的许多过程中起着至关重要的作用，如生长、抵御生物和非生物胁迫、脂质屏障沉积、有性生殖和信号传导。然而，PLTPs的结构和功能研究仍然缺乏，其生物学作用仍然难以捉摸。该项目旨在通过结合中子反射仪（NR）和分子动力学（MD）模拟来研究PLTP与自由浮动膜系统之间的相互作用，该系统由脂质混合物组成，准确代表高等植物膜的组成和流动性，从而获得对PLTP活性的分子见解。NR是一种强大的技术，用于获得动态膜结合过程的结构见解，因为它是一种非破坏性方法，使我们能够在生理条件下测量蛋白质向膜系统的添加。NR实验提供的结构信息可用于生成MD模拟的起始条件和参数，MD模拟在相互作用过程中产生膜和蛋白质结构的完全原子分辨率，从而使我们能够完善实验模型。解决了BBSRC优先领域的方法，以提高理解植物脂质转运蛋白，通过结合中子反射和分子动力学模拟解决了BBSRC的几个优先领域。特别地，通过使用和开发进一步的计算工具来改进和支持实验实现的结构模型的方法涉及“数据驱动生物学”和“生物科学的系统方法”的领域。获得植物膜相关现象的精确分子细节对我们理解植物中的广泛的生物化学过程（例如病原体相互作用）具有潜在的大的下游益处。细胞内稳态和调节。因此，该项目的见解可以导致新的植物处理策略，从而提高粮食生产效率。因此，“可持续地提高农业生产”这一优先领域也通过该项目得到解决。

Plant lipid transfer proteins (PLTPs) have the ability to bind and transport lipids and are considered as key proteins for plant survival on land. PLTPs play a crucial role in many processes in plants, such as growing, defence against biotic and abiotic stress, lipid barrier deposition, sexual reproduction and signalling. However, the structural and functional investigations of PLTPs are still lacking and their biological role remains elusive. This project aims to gain molecular insights into the activity of PLTPs by combining neutron reflectometry (NR) and molecular dynamic (MD) simulations to study the interaction between PLTPs with free floating membrane systems composed of lipid mixtures which accurately represent the compositions and fluidity of higher plant membranes. NR is a powerful technique for gaining structural insights into dynamic membrane binding processes as it is a nondestructive method which enables us to measure the addition of a protein to a membrane system at physiological conditions. The structural information provided by the NR experiments can be used to generate starting conditions and parameters for MD simulations, which produce a fully atomisticresolution of the membrane and protein structure during the interaction process, thereby enabling us to refine the experimental model.Addressed BBSRC Priority AreasThe approach to improve the understanding of plant lipid transfer proteins through the combination of neutron reflectometry and molecular dynamic simulations addresses several BBSRC priority areas. In particular, the approach to refine and support the experimental achieved structural models by using and developing further computational tools relates to the area of 'data driven biology' and 'systems approaches to the biosciences'.Gaining precise molecular details of plant membrane related phenomena has potential large downstream benefits to our understanding of a wide range of biochemical processes in plants such as pathogen interactions, cell homeostasis and regulation. Thus, the insights of this project can lead to new treatment strategies of plants and therefore improve the efficiency of food production. Hence, the priority area of 'Sustainably enhancing agricultural production' is also addressed through this project.