Title: Multi-scale structural analysis of proteins by deep semantic segmentation

Abstract

Abstract Motivation Recent advances in computational methods have facilitated large-scale sampling of protein structures, leading to breakthroughs in protein structural prediction and enabling de novo protein design. Establishing methods to identify candidate structures that can lead to native folds or designable structures remains a challenge, since few existing metrics capture high-level structural features such as architectures, folds and conformity to conserved structural motifs. Convolutional Neural Networks (CNNs) have been successfully used in semantic segmentation—a subfield of image classification in which a class label is predicted for every pixel. Here, we apply semantic segmentation to protein structures as a novel strategy for fold identification and structure quality assessment. Results We train a CNN that assigns each residue in a multi-domain protein to one of 38 architecture classes designated by the CATH database. Our model achieves a high per-residue accuracy of 90.8% on the test set (95.0% average per-class accuracy; 87.8% average per-structure accuracy). We demonstrate that individual class probabilities can be used as a metric that indicates the degree to which a randomly generated structure assumes a specific fold, as well as a metric that highlights non-conformative regions of a protein belonging to a known class. These capabilities yield a powerful tool for guidingmore » structural sampling for both structural prediction and design. Availability and implementation The trained classifier network, parser network, and entropy calculation scripts are available for download at https://git.io/fp6bd, with detailed usage instructions provided at the download page. A step-by-step tutorial for setup is provided at https://goo.gl/e8GB2S. All Rosetta commands, RosettaRemodel blueprints, and predictions for all datasets used in the study are available in the Supplementary Information. Supplementary information Supplementary data are available at Bioinformatics online.« less

Authors:

Eguchi, Raphael R. ^[1]; Huang, Po-Ssu ^[2]; Valencia, ed., Alfonso

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+ Show Author Affiliations

1. Department of Biochemistry, School of Medicine, Stanford University, Shriram Center for Bioengineering and Chemical Engineering, 443 via Ortega, Room 036, Stanford, CA 94305, USA
2. Department of Bioengineering, Schools of Engineering and Medicine, Stanford University Shriram Center for Bioengineering and Chemical Engineering, 443 via Ortega, Room 036, Stanford, CA 94305, USA

Publication Date:

2019-08-19

Sponsoring Org.:

USDOE

OSTI Identifier:

1604834

Resource Type:

Published Article

Journal Name:

Bioinformatics

Additional Journal Information:

Journal Name: Bioinformatics Journal Volume: 36 Journal Issue: 6; Journal ID: ISSN 1367-4803

Publisher:

Oxford University Press

Country of Publication:

United Kingdom

Language:

English