Integration of molecular coarse-grained model into geometric representation learning framework for protein-protein complex property prediction

Abstract Structure-based machine learning algorithms have been utilized to predict the properties of protein-protein interaction (PPI) complexes, such as binding affinity, which is critical for understanding biological mechanisms and disease treatments. While most existing algorithms represent PPI c...

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Main Authors: Yang Yue, Shu Li, Yihua Cheng, Lie Wang, Tingjun Hou, Zexuan Zhu, Shan He
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-53583-w
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author Yang Yue
Shu Li
Yihua Cheng
Lie Wang
Tingjun Hou
Zexuan Zhu
Shan He
author_facet Yang Yue
Shu Li
Yihua Cheng
Lie Wang
Tingjun Hou
Zexuan Zhu
Shan He
author_sort Yang Yue
collection DOAJ
description Abstract Structure-based machine learning algorithms have been utilized to predict the properties of protein-protein interaction (PPI) complexes, such as binding affinity, which is critical for understanding biological mechanisms and disease treatments. While most existing algorithms represent PPI complex graph structures at the atom-scale or residue-scale, these representations can be computationally expensive or may not sufficiently integrate finer chemical-plausible interaction details for improving predictions. Here, we introduce MCGLPPI, a geometric representation learning framework that combines graph neural networks (GNNs) with MARTINI molecular coarse-grained (CG) models to predict PPI overall properties accurately and efficiently. Extensive experiments on three types of downstream PPI property prediction tasks demonstrate that at the CG-scale, MCGLPPI achieves competitive performance compared with the counterparts at the atom- and residue-scale, but with only a third of computational resource consumption. Furthermore, CG-scale pre-training on protein domain-domain interaction structures enhances its predictive capabilities for PPI tasks. MCGLPPI offers an effective and efficient solution for PPI overall property predictions, serving as a promising tool for the large-scale analysis of biomolecular interactions.
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issn 2041-1723
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spelling doaj-art-58efcb3b577b42d5bc3ea273c6d791742025-08-20T02:13:55ZengNature PortfolioNature Communications2041-17232024-11-0115111410.1038/s41467-024-53583-wIntegration of molecular coarse-grained model into geometric representation learning framework for protein-protein complex property predictionYang Yue0Shu Li1Yihua Cheng2Lie Wang3Tingjun Hou4Zexuan Zhu5Shan He6School of Computer Science, The University of Birmingham, EdgbastonMacao Polytechnic UniversitySchool of Computer Science, The University of Birmingham, EdgbastonBone Marrow Transplantation Center of the First Affiliated Hospital, Institute of Immunology, Zhejiang University School of MedicineCollege of Pharmaceutical Sciences, Zhejiang UniversityNational Engineering Laboratory for Big Data System Computing Technology, Shenzhen UniversitySchool of Computer Science, The University of Birmingham, EdgbastonAbstract Structure-based machine learning algorithms have been utilized to predict the properties of protein-protein interaction (PPI) complexes, such as binding affinity, which is critical for understanding biological mechanisms and disease treatments. While most existing algorithms represent PPI complex graph structures at the atom-scale or residue-scale, these representations can be computationally expensive or may not sufficiently integrate finer chemical-plausible interaction details for improving predictions. Here, we introduce MCGLPPI, a geometric representation learning framework that combines graph neural networks (GNNs) with MARTINI molecular coarse-grained (CG) models to predict PPI overall properties accurately and efficiently. Extensive experiments on three types of downstream PPI property prediction tasks demonstrate that at the CG-scale, MCGLPPI achieves competitive performance compared with the counterparts at the atom- and residue-scale, but with only a third of computational resource consumption. Furthermore, CG-scale pre-training on protein domain-domain interaction structures enhances its predictive capabilities for PPI tasks. MCGLPPI offers an effective and efficient solution for PPI overall property predictions, serving as a promising tool for the large-scale analysis of biomolecular interactions.https://doi.org/10.1038/s41467-024-53583-w
spellingShingle Yang Yue
Shu Li
Yihua Cheng
Lie Wang
Tingjun Hou
Zexuan Zhu
Shan He
Integration of molecular coarse-grained model into geometric representation learning framework for protein-protein complex property prediction
Nature Communications
title Integration of molecular coarse-grained model into geometric representation learning framework for protein-protein complex property prediction
title_full Integration of molecular coarse-grained model into geometric representation learning framework for protein-protein complex property prediction
title_fullStr Integration of molecular coarse-grained model into geometric representation learning framework for protein-protein complex property prediction
title_full_unstemmed Integration of molecular coarse-grained model into geometric representation learning framework for protein-protein complex property prediction
title_short Integration of molecular coarse-grained model into geometric representation learning framework for protein-protein complex property prediction
title_sort integration of molecular coarse grained model into geometric representation learning framework for protein protein complex property prediction
url https://doi.org/10.1038/s41467-024-53583-w
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