Machine learning in computational modelling of membrane protein sequences and structures: From methodologies to applications

Membrane proteins mediate a wide spectrum of biological processes, such as signal transduction and cell communication. Due to the arduous and costly nature inherent to the experimental process, membrane proteins have long been devoid of well-resolved atomic-level tertiary structures and, consequently, the understanding of their functional roles underlying a multitude of life activities has been hampered. Currently, computational tools dedicated to furthering the structure-function understanding are primarily focused on utilizing intelligent algorithms to address a variety of site-wise prediction problems (e.g., to-pology and interaction sites), but are scattered across different computing sources. Moreover, the recent advent of deep learning techniques has immensely expedited the development of computational tools for membrane protein-related prediction problems. Given the growing number of applications optimized particularly by manifold deep neural networks, we herein provide a review on the current status of com-putational strategies mainly in membrane protein type classification, topology identification, interaction site detection, and pathogenic effect prediction. Meanwhile, we provide an overview of how the entire prediction process proceeds, including database collection, data pre-processing, feature extraction, and method selection. This review is expected to be useful for developing more extendable computational tools specific to membrane proteins.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).

Automated summary

Membrane proteins play crucial roles in various biological processes, but their atomic-level structures are difficult to obtain. Computational tools utilizing intelligent algorithms and deep learning techniques have greatly advanced the prediction of membrane proteins. This review provides an overview of current computational strategies in membrane protein classification, topology identification, interaction site detection, and pathogenic effect prediction, as well as the prediction process itself.