Protein Structure Prediction: Conventional and Deep Learning Perspectives

Abstract

Protein structure prediction is a way to bridge the sequence-structure gap, one of the main challenges in computational biology and chemistry. Predicting any protein's accurate structure is of paramount importance for the scientific community, as these structures govern their function. Moreover, this is one of the complicated optimization problems that computational biologists have ever faced. Experimental protein structure determination methods include X-ray crystallography, Nuclear Magnetic Resonance Spectroscopy and Electron Microscopy. All of these are tedious and time-consuming procedures that require expertise. To make the process less cumbersome, scientists use predictive tools as part of computational methods, using data consolidated in the protein repositories. In recent years, machine learning approaches have raised the interest of the structure prediction community. Most of the machine learning approaches for protein structure prediction are centred on co-evolution based methods. The accuracy of these approaches depends on the number of homologous protein sequences available in the databases. The prediction problem becomes challenging for many proteins, especially those without enough sequence homologs. Deep learning methods allow for the extraction of intricate features from protein sequence data without making any intuitions. Accurately predicted protein structures are employed for drug discovery, antibody designs, understanding protein-protein interactions, and interactions with other molecules. This article provides a review of conventional and deep learning approaches in protein structure prediction. We conclude this review by outlining a few publicly available datasets and deep learning architectures currently employed for protein structure prediction tasks.

Keywords: Ab-initio; CNN; Deep learning; Fragment-based approaches; Homology modeling; LSTM; Protein structure prediction; Proteins; Self-supervised learning; Template-based modeling; Tertiary structure; Threading; Transformers.