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Ab-Initio Membrane Protein Amphipathic Helix Structure Prediction Using Deep Neural Networks

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Amphipathic helix (AH)features the segregation of polar and nonpolar residues and plays important roles in many membrane-associated biological processes through interacting with both the lipid and the soluble phases. Although… Click to show full abstract

Amphipathic helix (AH)features the segregation of polar and nonpolar residues and plays important roles in many membrane-associated biological processes through interacting with both the lipid and the soluble phases. Although the AH structure has been discovered for a long time, few ab initio machine learning-based prediction models have been reported, due to the limited amount of training data. In this study, we report a new deep learning-based prediction model, which is composed of a residual neural network and the uneven-thresholds decision algorithm. It is constructed on 121 membrane proteins, in total 51640 residue samples, which are curated from an up-to-date membrane protein structure database. Through a rigid 10-fold nested cross-validation experiment, we demonstrate that our model can achieve promising predictions and exceed current state-of-the-art approaches in this field. This presents a new avenue for accurately predicting AHs. Analysis on the contribution of the input residues and some cases further reveals the high interpretability and the generalization of our model.

Keywords: amphipathic helix; structure; prediction; membrane protein

Journal Title: IEEE/ACM Transactions on Computational Biology and Bioinformatics
Year Published: 2022

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