Development and assessment of methods for membrane protein structure prediction

我们开发了一种新的计算机软件，用于精确比较完整膜蛋白的序列。该软件名为AlignMe，通过结合膜蛋白特异性特征（如疏水性和跨膜螺旋预测），以及标准属性（如二级结构）和同源序列集合的进化概况来计算序列比对。AlignMe可以根据比对的难度（即两个序列的相似性）在许多不同的模式下使用，并且在非常远同源的情况下特别有用，因为它结合了序列，二级结构和跨膜跨度预测，有助于指导两个蛋白质序列的比对。此外，由于我们使用一组已知的膜蛋白结构作为间隙惩罚参数训练的参考，因此所有AlignMe模式都可以完美地调整为对准膜蛋白序列。

We developed novel computer software for accurate comparison of the sequences of integral membrane proteins. The software, called AlignMe, computes sequence alignments by incorporation of membrane-protein-specific features such as hydrophobicity and transmembrane helix predictions, along with standard properties such as secondary structure, and evolutionary profiles from collections of homologous sequences M Stamm, R Staritzbichler, K Khafizov and LR Forrest, PLoS One 8(3):57731, 2013. AlignMe can be used in a number of different modes depending on the difficulty of the alignment (i.e., the similarity of the two sequences), and is particularly helpful in cases of very remote homology, because it combines sequence, secondary structure and transmembrane span predictions that help to guide the alignment of the two protein sequences. Moreover, because we use a set of known membrane protein structures as references for training of the gap penalty parameters, all AlignMe modes are perfectly tuned to aligning membrane protein sequences. We recently made the AlignMe software available via a web server hosted at www.alignme.org, providing a user-friendly interface to a diverse array of functionalities 1. The code, written in C++, can also be downloaded from that webpage and installed locally on any Unix-based platform. Notably, the AlignMe server now also provides a platform for aligning of hydropathy profiles, providing open access to a technique that was formerly only available in one or two specialized labs, but which has proven useful in a number of studies for comparison of transmembrane topologies of putatively-related proteins, including for identifying structural repeats C Fenollar-Ferrer, M Patti, T Knoepfel, A Werner, IC Forster, and LR Forrest, Biophys J 106:1268-1279, 2014; K Khafizov, R Staritzbichler, M Stamm and LR Forrest, Biochemistry 49:10702-10713, 2010.