Affiliation:
1. Science for Life Laboratory and Department of Biochemistry and Biophysics, Stockholm University, 171 21 Solna, Sweden
2. Center for Computational Biology, The University of Kansas, Lawrence, KS 66047, USA
Abstract
Abstract
Motivation
In the last decade, de novo protein structure prediction accuracy for individual proteins has improved significantly by utilising deep learning (DL) methods for harvesting the co-evolution information from large multiple sequence alignments (MSAs). The same approach can, in principle, also be used to extract information about evolutionary-based contacts across protein–protein interfaces. However, most earlier studies have not used the latest DL methods for inter-chain contact distance prediction. This article introduces a fold-and-dock method based on predicted residue-residue distances with trRosetta.
Results
The method can simultaneously predict the tertiary and quaternary structure of a protein pair, even when the structures of the monomers are not known. The straightforward application of this method to a standard dataset for protein–protein docking yielded limited success. However, using alternative methods for generating MSAs allowed us to dock accurately significantly more proteins. We also introduced a novel scoring function, PconsDock, that accurately separates 98% of correctly and incorrectly folded and docked proteins. The average performance of the method is comparable to the use of traditional, template-based or ab initio shape-complementarity-only docking methods. Moreover, the results of conventional and fold-and-dock approaches are complementary, and thus a combined docking pipeline could increase overall docking success significantly. This methodology contributed to the best model for one of the CASP14 oligomeric targets, H1065.
Availability and implementation
All scripts for predictions and analysis are available from https://github.com/ElofssonLab/bioinfo-toolbox/ and https://gitlab.com/ElofssonLab/benchmark5/. All models joined alignments, and evaluation results are available from the following figshare repository https://doi.org/10.6084/m9.figshare.14654886.v2.
Supplementary information
Supplementary data are available at Bioinformatics online.
Funder
Swedish National Research Council
Swedish Research Council partly paid the salary
Publisher
Oxford University Press (OUP)
Subject
Computational Mathematics,Computational Theory and Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Statistics and Probability
Cited by
12 articles.
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