Sixty-five years of the long march in protein secondary structure prediction: the final stretch?

• Published in: Briefings in bioinformatics Vol. 19; no. 3; pp. 482 - 494
• Main Authors: Yang, Yuedong, Gao, Jianzhao, Wang, Jihua, Heffernan, Rhys, Hanson, Jack, Paliwal, Kuldip, Zhou, Yaoqi
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2018; Oxford Publishing Limited (England)
• Subjects: Algorithms; amino acid sequences; Backbone; Cattle; Computational Biology - methods; Databases, Protein; Deep learning; Humans; Machine learning; methodology; Models, Theoretical; Neural Networks, Computer; polypeptides; prediction; Predictions; protein secondary structure; Protein structure; Protein Structure, Secondary; Proteins; Proteins - chemistry; Secondary structure; Torsion; torsion angle prediction; backbone structure prediction; secondary structure prediction; deep neural networks; machine learning
• ISSN: 1467-5463; 1477-4054; 1477-4054
• DOI: 10.1093/bib/bbw129

Abstract Protein secondary structure prediction began in 1951 when Pauling and Corey predicted helical and sheet conformations for protein polypeptide backbone even before the first protein structure was determined. Sixty-five years later, powerful new methods breathe new life into this field. The highest three-state accuracy without relying on structure templates is now at 82-84%, a number unthinkable just a few years ago. These improvements came from increasingly larger databases of protein sequences and structures for training, the use of template secondary structure information and more powerful deep learning techniques. As we are approaching to the theoretical limit of three-state prediction (88-90%), alternative to secondary structure prediction (prediction of backbone torsion angles and Cα-atom-based angles and torsion angles) not only has more room for further improvement but also allows direct prediction of three-dimensional fragment structures with constantly improved accuracy. About 20% of all 40-residue fragments in a database of 1199 non-redundant proteins have <6 Å root-mean-squared distance from the native conformations by SPIDER2. More powerful deep learning methods with improved capability of capturing long-range interactions begin to emerge as the next generation of techniques for secondary structure prediction. The time has come to finish off the final stretch of the long march towards protein secondary structure prediction.