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Accurate prediction of inter-protein residue–residue contacts for homo-oligomeric protein complexes

Protein–protein interactions play a fundamental role in all cellular processes. Therefore, determining the structure of protein–protein complexes is crucial to understand their molecular mechanisms and develop drugs targeting the protein–protein interactions. Recently, deep learning has led to a bre...

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Detalles Bibliográficos
Autores principales: Yan, Yumeng, Huang, Sheng-You
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425427/
https://www.ncbi.nlm.nih.gov/pubmed/33693482
http://dx.doi.org/10.1093/bib/bbab038
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author Yan, Yumeng
Huang, Sheng-You
author_facet Yan, Yumeng
Huang, Sheng-You
author_sort Yan, Yumeng
collection PubMed
description Protein–protein interactions play a fundamental role in all cellular processes. Therefore, determining the structure of protein–protein complexes is crucial to understand their molecular mechanisms and develop drugs targeting the protein–protein interactions. Recently, deep learning has led to a breakthrough in intra-protein contact prediction, achieving an unusual high accuracy in recent Critical Assessment of protein Structure Prediction (CASP) structure prediction challenges. However, due to the limited number of known homologous protein–protein interactions and the challenge to generate joint multiple sequence alignments of two interacting proteins, the advances in inter-protein contact prediction remain limited. Here, we have proposed a deep learning model to predict inter-protein residue–residue contacts across homo-oligomeric protein interfaces, named as DeepHomo. Unlike previous deep learning approaches, we integrated intra-protein distance map and inter-protein docking pattern, in addition to evolutionary coupling, sequence conservation, and physico-chemical information of monomers. DeepHomo was extensively tested on both experimentally determined structures and realistic CASP-Critical Assessment of Predicted Interaction (CAPRI) targets. It was shown that DeepHomo achieved a high precision of >60% for the top predicted contact and outperformed state-of-the-art direct-coupling analysis and machine learning-based approaches. Integrating predicted inter-chain contacts into protein–protein docking significantly improved the docking accuracy on the benchmark dataset of realistic homo-dimeric targets from CASP-CAPRI experiments. DeepHomo is available at http://huanglab.phys.hust.edu.cn/DeepHomo/
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spelling pubmed-84254272021-09-09 Accurate prediction of inter-protein residue–residue contacts for homo-oligomeric protein complexes Yan, Yumeng Huang, Sheng-You Brief Bioinform Problem Solving Protocol Protein–protein interactions play a fundamental role in all cellular processes. Therefore, determining the structure of protein–protein complexes is crucial to understand their molecular mechanisms and develop drugs targeting the protein–protein interactions. Recently, deep learning has led to a breakthrough in intra-protein contact prediction, achieving an unusual high accuracy in recent Critical Assessment of protein Structure Prediction (CASP) structure prediction challenges. However, due to the limited number of known homologous protein–protein interactions and the challenge to generate joint multiple sequence alignments of two interacting proteins, the advances in inter-protein contact prediction remain limited. Here, we have proposed a deep learning model to predict inter-protein residue–residue contacts across homo-oligomeric protein interfaces, named as DeepHomo. Unlike previous deep learning approaches, we integrated intra-protein distance map and inter-protein docking pattern, in addition to evolutionary coupling, sequence conservation, and physico-chemical information of monomers. DeepHomo was extensively tested on both experimentally determined structures and realistic CASP-Critical Assessment of Predicted Interaction (CAPRI) targets. It was shown that DeepHomo achieved a high precision of >60% for the top predicted contact and outperformed state-of-the-art direct-coupling analysis and machine learning-based approaches. Integrating predicted inter-chain contacts into protein–protein docking significantly improved the docking accuracy on the benchmark dataset of realistic homo-dimeric targets from CASP-CAPRI experiments. DeepHomo is available at http://huanglab.phys.hust.edu.cn/DeepHomo/ Oxford University Press 2021-03-05 /pmc/articles/PMC8425427/ /pubmed/33693482 http://dx.doi.org/10.1093/bib/bbab038 Text en © The Author(s) 2021. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Problem Solving Protocol
Yan, Yumeng
Huang, Sheng-You
Accurate prediction of inter-protein residue–residue contacts for homo-oligomeric protein complexes
title Accurate prediction of inter-protein residue–residue contacts for homo-oligomeric protein complexes
title_full Accurate prediction of inter-protein residue–residue contacts for homo-oligomeric protein complexes
title_fullStr Accurate prediction of inter-protein residue–residue contacts for homo-oligomeric protein complexes
title_full_unstemmed Accurate prediction of inter-protein residue–residue contacts for homo-oligomeric protein complexes
title_short Accurate prediction of inter-protein residue–residue contacts for homo-oligomeric protein complexes
title_sort accurate prediction of inter-protein residue–residue contacts for homo-oligomeric protein complexes
topic Problem Solving Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425427/
https://www.ncbi.nlm.nih.gov/pubmed/33693482
http://dx.doi.org/10.1093/bib/bbab038
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