Orientations of Proteins in Membranes: Tools and Database

位于安娜堡的密歇根大学获得了一笔拨款，用于开发计算工具和数据库，用于膜相关肽和蛋白质的结构研究、建模和比较分析。细胞中一半以上的蛋白质与细胞膜相互作用。这些蛋白质不是单独起作用，而是作为浸泡在磷脂基质中的大的多蛋白质复合物起作用。虽然生物膜的许多单独成分在原子水平上得到了很好的研究，但人们对膜作为超分子组件的空间组织和功能知之甚少。特别是，脂质双分子层的空间位置仅对沉积在蛋白质数据库（PDB）中的数千种膜相关蛋白中的几十种进行了实验研究。为了填补这一空白，最近开发了一种快速计算方法来确定膜中蛋白质的最佳旋转和平移位置。该方法将被扩展、改进和适应于PDB中膜相关蛋白的自动化大规模分析和单跨膜蛋白的α -螺旋结构域的建模。计算工具将包括用于定位膜中蛋白质（PPM 2.0）和膜相关肽折叠（FMAP）的软件，以及下一代膜中蛋白质取向（OPM）数据库（http://opm.phar.umich.edu）。扩展后的OPM数据库将保存数千个跨膜和外周肽和蛋白质的三维结构。它将提供蛋白质相对于脂质双分子层的计算空间位置，膜蛋白在进化相关家族中的分类，以及它们的亚细胞定位，拓扑结构，生物来源，功能数据，交互式可视化工具和与其他生物信息学资源的链接。这些工具和扩展的数据库将满足膜蛋白质组学、脂质组学、生物物理学、生物化学和细胞生物学等领域的研究人员的需要。它们对于膜肽和膜蛋白的比较进化分析、实验诱变研究和从头设计至关重要。计划中的资源也将对教学非常有价值，并将加强密歇根大学和世界其他学校的药物化学和生物信息学课程。数据的图形化表示和可视化工具对于高中和大学本科学生的教学以及一般公众来说特别有用。

The University of Michigan in Ann Arbor has received a grant to develop computational tools and a database for structural studies, modeling and comparative analysis of membrane-associated peptides and proteins. More than half of all proteins in cells interact with membranes. These proteins do not function individually but as large multi-protein complexes immersed in the phospholipid matrix. Although many individual components of biological membranes are well studied at the atomic level, little is known about the spatial organization and the function of membranes as supra-molecular assemblies. In particular, the spatial positions in the lipid bilayer have been experimentally studied only for a few dozen out of several thousands of membrane-associated proteins deposited in the Protein Data Bank (PDB). To fill this gap, a fast computational method to determine the optimal rotational and translational positions of proteins in membranes has recently been developed. This method will be extended, improved and adapted for the automated large-scale analysis of membrane-associated proteins from the PDB and for modeling alpha-helical domains of single-spanning transmembrane proteins. The computational tools will include software for positioning proteins in membranes (PPM 2.0) and folding of membrane-associated peptides (FMAP), as well as the next generation of the Orientations of Proteins in Membranes (OPM) database (http://opm.phar.umich.edu). The expanded OPM database will hold several thousand three-dimensional structures of transmembrane and peripheral peptides and proteins. It will provide the calculated spatial positions of the proteins with respect to the lipid bilayer, classification of membrane proteins into evolutionarily related families, along with their subcellular localization, topology, biological source, functional data, interactive visualization tools and links to other bioinformatics resources. These tools and the expanded database will satisfy the needs of researchers who work in the field of membrane proteomics, lipidomics, biophysics, biochemistry and cell biology. They are vital for the comparative evolutionary analysis, experimental mutagenesis studies and de novo design of membrane peptides and proteins. The planned resources will also be very valuable for teaching and will enhance the Medicinal Chemistry and bioinformatics curriculum at University of Michigan and other schools worldwide. The graphical representation of data and visualization tools will be especially useful for teaching high school and undergraduate college students, as well as for the general public.