An Improved Topology Prediction of Alpha-Helical Transmembrane Protein Based on Deep Multi-Scale Convolutional Neural Network.

Abstract

Alpha-helical proteins ( αTMPs) are essential in various biological processes. Despite their tertiary structures are crucial for revealing complex functions, experimental structure determination remains challenging and costly. In the past decades, various sequence-based topology prediction methods have been developed to bridge the gap between the sequences and structures by characterizing the structural features, but significant improvements are still required. Deep learning brings a great opportunity for its powerful representation learning capability from limited original data. In this work, we improved our αTMP topology prediction method DMCTOP using deep learning, which composed of two deep convolutional blocks to simultaneously extract local and global contextual features. Consequently, the inputs were simplified to reflect the original features of the sequence, including a protein sequence feature and an evolutionary conservation feature. DMCTOP can efficiently and accurately identify all topological types and the N-terminal orientation for an αTMP sequence. To validate the effectiveness of our method, we benchmarked DMCTOP against 13 peer methods according to the whole sequence, the transmembrane segment and the traditional criterion in testing experiments. All the results reveal that our method achieved the highest prediction accuracy and outperformed all the previous methods. The method is available at https://icdtools.nenu.edu.cn/dmctop.