Collaborative Research: ABI Development: Development and Application of Graphical User Interfaces for System Building and Analysis of Membrane Simulations

该合作项目旨在开发图形用户界面（GUI），允许专家和非专家用户轻松设置，执行和分析各种膜模拟。这些工具集将大大减少学习曲线，这通常会阻止非专家利用模拟来研究膜系统。基于CHARMM-GUI中的Membrane Builder软件（www.charmm-gui.org/input/membrane），该项目有三个具体目标。在AIM 1中，将开发一个跨平台、独立的GUI工具集，用于分析来自各种模拟程序（包括CHARMM、Amber、GROMACS和NAMD）的膜模拟轨迹。在AIM 2中，Membrane Builder将通过以下方式进一步开发：（i）包含更多（生物学上重要的）脂质分子，（ii）开发构建单层、胶束和囊泡系统的工具，（iii）为GROMACS和Amber包提供模拟输入（Membrane Builder目前为CHARMM和NAMD计划提供输入）。在AIM 3中，膜构建器/分析仪将用于研究（i）链饱和度、链长、胆固醇浓度和脂质头基对脂质性质的影响，（ii）含磷酸肌醇信号脂质的膜，以及（iii）含鞘脂和胆固醇的膜。这些研究还将提供脂质结构库以及这些膜的平衡系统，以促进在Membrane Builder中构建混合脂质系统。生物膜和膜相关蛋白质/肽在许多细胞过程（营养物质的运输和促进细胞内功能）和生物工程/生物技术（疫苗/药物的可能载体和用于膜技术评估的固体支持脂质单层模型）中起着重要作用。因此，从原子细节上研究与脂膜和膜蛋白有关的现象一直是人们极大的兴趣。分子动力学模拟（探测分子功能的时间进程）在理解膜蛋白的动力学和潜在能量学方面特别有用，这很难单独从实验数据中提取。因此，膜和膜蛋白的计算建模和模拟可以补充在分子/原子水平上理解其结构和功能的实验。该项目旨在通过为广泛的研究背景和多个模拟社区的学生和研究人员提供任何一般膜或膜蛋白模拟的Membrane Builder/Analyzer GUI资源来促进协同科学研究和教育。特别是，该团队将组织一个研讨会，直接与用户社区互动，并为当地高中生开发一个暑期项目，提供使用膜构建器/分析器进行膜模拟的研究经验。

This collaborative project aims to develop graphical user interfaces (GUIs) that allow both expert and non-expert users to easily setup, perform, and analyze various membrane simulations. These toolsets will greatly reduce the learning curve that typically prevents non-experts from utilizing simulations to study membrane systems. Based on the Membrane Builder software in CHARMM-GUI (www.charmm-gui.org/input/membrane), the project has three specific aims. In AIM 1, a cross-platform, standalone GUI toolset will be developed to perform analyses of membrane simulation trajectories from various simulation programs including CHARMM, Amber, GROMACS, and NAMD. In AIM 2, Membrane Builder will be further developed by (i) including more (biologically important) lipid molecules, (ii) developing tools to build monolayer, micelle, and vesicle systems, (iii) providing simulation inputs for GROMACS and Amber packages (Membrane Builder currently provides the inputs for CHARMM and NAMD programs). In AIM 3, Membrane Builder/Analyzer will be used to study (i) the influences of chain saturation, chain length, cholesterol concentration, and lipid head groups on lipid properties, (ii) membranes with the phosphoinositol signaling lipid, and (iii) membranes with sphingolipids and cholesterol. Such studies will also provide the lipid structural libraries as well as the equilibrated systems of these membranes to facilitate the building of mixed lipid systems in Membrane Builder. Membrane Builder/Membrane Analyzer will be hosted in the CHARMM-GUI web server.Biological membranes and membrane-associated proteins/peptides play important roles in many cellular processes (transport of nutrients and facilitating function within the cell) and in bioengineering / biotechnology (possible vehicles for vaccines/drugs and models for solid-support lipid monolayers for technological assessment of membranes). Therefore, studying the phenomena related to lipid membranes and membrane proteins in atomic detail has been of great interest. Molecular dynamics simulations (time progression of molecules to probe their function) have been particularly useful in understanding the dynamics and the underlying energetics of membrane proteins, which is difficult to extract from experimental data alone. Thus, computational modeling and simulations of membranes and membrane proteins can supplement experiments in understanding their structure and function at the molecular/atomic level. This project seeks to foster synergistic scientific research and education by providing the Membrane Builder/Analyzer GUI resources for any general membrane or membrane protein simulations to students and researchers in a wide array of research contexts and multiple simulation communities. In particular, the team will organize a workshop to directly interact with the user community, and also develop a summer program for local high school students to provide research experience in membrane simulations using Membrane Builder/Analyzer.