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-图形用户界面中的膜生成器软件(www.charmm-gui.org/INPUT/MEMBER)，该项目有三个具体目标。在AIM 1中，将开发一个跨平台、独立的图形用户界面工具集，以执行各种模拟程序(包括CHARMM、AMBER、GROMACS和NAMD)的膜模拟轨迹分析。在AIM 2中，膜生成器将通过(I)包括更多(生物学上重要的)脂分子，(Ii)开发构建单层、胶束和囊泡系统的工具，(Iii)为GROMACS和琥珀包提供模拟输入(膜生成器目前为CHARMM和NAMD程序提供输入)来进一步开发。在AIM 3中，膜生成器/分析仪将用于研究(I)链饱和度、链长度、胆固醇浓度和脂头基团对脂类性质的影响，(Ii)含有磷肌醇信号脂质的膜，以及(Iii)含有鞘磷脂和胆固醇的膜。这些研究还将提供脂类结构库以及这些膜的平衡系统，以促进在膜生成器中建立混合脂类系统。膜生成器/膜分析器将安装在CHARMM-GUIWeb服务器中。生物膜和膜相关蛋白/肽在许多细胞过程(营养物质的运输和促进细胞内的功能)和生物工程/生物技术(可能用于疫苗/药物的载体和用于膜的技术评估的固体支持脂单分子层的模型)中发挥重要作用。因此，从原子细节上研究与脂膜和膜蛋白相关的现象具有重要的意义。分子动力学模拟(探索其功能的分子的时间进程)在理解膜蛋白的动力学和潜在的能量学方面特别有用，而膜蛋白的动力学和潜在的能量学很难仅从实验数据中提取。因此，膜和膜蛋白的计算建模和模拟可以补充实验在分子/原子水平上理解它们的结构和功能。该项目致力于通过在广泛的研究背景和多个模拟社区中向学生和研究人员提供任何一般膜或膜蛋白模拟的膜生成器/分析器图形用户界面资源来促进协同科学研究和教育。特别是，该团队将组织一次研讨会，直接与用户社区互动，并为当地高中生开发一个暑期计划，提供使用膜生成器/分析仪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.