Transmembrane helix prediction: a comparative evaluation and analysis
Transmembrane helix prediction: a comparative evaluation and analysis
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DOI：
10.1093/protein/gzi032
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发表时间：
2005-06-01
影响因子：
2.4
通讯作者：
Sansom, MSP
中科院分区：
文献类型：
--
作者：
Cuthbertson, JM;Doyle, DA;Sansom, MSP
跨膜（TM）螺旋的预测在膜蛋白的研究中起着重要的作用，因为这类蛋白质的高分辨率结构相对较少（约为PDB的0.5%）。我们使用了两个数据集（一个冗余和一个非冗余）的高分辨率结构的膜蛋白来评估和分析TM螺旋预测。冗余（非冗余）数据集包含来自112（73）条多肽链的434（268）个TM螺旋的结构。在数据集中的434个螺旋中，20个可以被分类为“半TM”，因为它们太短而不能跨越脂质双层。我们比较了13种TM螺旋预测方法，使用每个片段、每个残基和末端评分来评估每种方法。四种方法始终表现良好：SPLIT 4、TMHMM 2、HMMTOP 2和TMAP。然而，即使是最好的方法，在TM螺旋末端平均也有大约两圈螺旋的误差。分析了单个蛋白质的最佳和最差情况预测。特别是，各种方法和一致性预测方法的性能进行了比较，为一些蛋白质（如SecY，CIC，KvAP）含有半TM螺旋。预测半TM螺旋的困难表明，目前的预测方法成功地体现了膜蛋白折叠的双态模型，但不适应第三阶段，其中，例如，短螺旋和折返环折叠在一束稳定的TM螺旋内。
The prediction of transmembrane (TM) helices plays an important role in the study of membrane proteins, given the relatively small number (similar to 0.5% of the PDB) of high-resolution structures for such proteins. We used two datasets (one redundant and one non-redundant) of high-resolution structures of membrane proteins to evaluate and analyse TM helix prediction. The redundant (non-redundant) dataset contains structure of 434 (268) TM helices, from 112 (73) polypeptide chains. Of the 434 helices in the dataset, 20 may be classified as 'half-TM' as they are too short to span a lipid bilayer. We compared 13 TM helix prediction methods, evaluating each method using per segment, per residue and termini scores. Four methods consistently performed well: SPLIT4, TMHMM2, HMMTOP2 and TMAP. However, even the best methods were in error by, on average, about two turns of helix at the TM helix termini. The best and worst case predictions for individual proteins were analysed. In particular, the performance of the various methods and of a consensus prediction method, were compared for a number of proteins (e.g. SecY, CIC, KvAP) containing half-TM helices. The difficulties of predicting half-TM helices suggests that current prediction methods successfully embody the two-state model of membrane protein folding, but do not accommodate a third stage in which, e.g., short helices and re-entrant loops fold within a bundle of stable TM helices.