{"title":"利用几何注意力、分辨率间转移学习和基于同源性的增强技术,加速蛋白质结合位点预测。","authors":"Daeseok Lee, Wonjun Hwang, Jeunghyun Byun, Bonggun Shin","doi":"10.1186/s12859-024-05923-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Locating small molecule binding sites in target proteins, in the resolution of either pocket or residue, is critical in many drug-discovery scenarios. Since it is not always easy to find such binding sites using conventional methods, different deep learning methods to predict binding sites out of protein structures have been developed in recent years. The existing deep learning based methods have several limitations, including (1) the inefficiency of the CNN-only architecture, (2) loss of information due to excessive post-processing, and (3) the under-utilization of available data sources.</p><p><strong>Methods: </strong>We present a new model architecture and training method that resolves the aforementioned problems. First, by layering geometric self-attention units on top of residue-level 3D CNN outputs, our model overcomes the problems of CNN-only architectures. Second, by configuring the fundamental units of computation as residues and pockets instead of voxels, our method reduced the information loss from post-processing. Lastly, by employing inter-resolution transfer learning and homology-based augmentation, our method maximizes the utilization of available data sources to a significant extent.</p><p><strong>Results: </strong>The proposed method significantly outperformed all state-of-the-art baselines regarding both resolutions-pocket and residue. An ablation study demonstrated the indispensability of our proposed architecture, as well as transfer learning and homology-based augmentation, for achieving optimal performance. We further scrutinized our model's performance through a case study involving human serum albumin, which demonstrated our model's superior capability in identifying multiple binding sites of the protein, outperforming the existing methods.</p><p><strong>Conclusions: </strong>We believe that our contribution to the literature is twofold. Firstly, we introduce a novel computational method for binding site prediction with practical applications, substantiated by its strong performance across diverse benchmarks and case studies. Secondly, the innovative aspects in our method- specifically, the design of the model architecture, inter-resolution transfer learning, and homology-based augmentation-would serve as useful components for future work.</p>","PeriodicalId":8958,"journal":{"name":"BMC Bioinformatics","volume":"25 1","pages":"306"},"PeriodicalIF":2.9000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416008/pdf/","citationCount":"0","resultStr":"{\"title\":\"Turbocharging protein binding site prediction with geometric attention, inter-resolution transfer learning, and homology-based augmentation.\",\"authors\":\"Daeseok Lee, Wonjun Hwang, Jeunghyun Byun, Bonggun Shin\",\"doi\":\"10.1186/s12859-024-05923-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Locating small molecule binding sites in target proteins, in the resolution of either pocket or residue, is critical in many drug-discovery scenarios. Since it is not always easy to find such binding sites using conventional methods, different deep learning methods to predict binding sites out of protein structures have been developed in recent years. The existing deep learning based methods have several limitations, including (1) the inefficiency of the CNN-only architecture, (2) loss of information due to excessive post-processing, and (3) the under-utilization of available data sources.</p><p><strong>Methods: </strong>We present a new model architecture and training method that resolves the aforementioned problems. First, by layering geometric self-attention units on top of residue-level 3D CNN outputs, our model overcomes the problems of CNN-only architectures. Second, by configuring the fundamental units of computation as residues and pockets instead of voxels, our method reduced the information loss from post-processing. Lastly, by employing inter-resolution transfer learning and homology-based augmentation, our method maximizes the utilization of available data sources to a significant extent.</p><p><strong>Results: </strong>The proposed method significantly outperformed all state-of-the-art baselines regarding both resolutions-pocket and residue. An ablation study demonstrated the indispensability of our proposed architecture, as well as transfer learning and homology-based augmentation, for achieving optimal performance. We further scrutinized our model's performance through a case study involving human serum albumin, which demonstrated our model's superior capability in identifying multiple binding sites of the protein, outperforming the existing methods.</p><p><strong>Conclusions: </strong>We believe that our contribution to the literature is twofold. Firstly, we introduce a novel computational method for binding site prediction with practical applications, substantiated by its strong performance across diverse benchmarks and case studies. Secondly, the innovative aspects in our method- specifically, the design of the model architecture, inter-resolution transfer learning, and homology-based augmentation-would serve as useful components for future work.</p>\",\"PeriodicalId\":8958,\"journal\":{\"name\":\"BMC Bioinformatics\",\"volume\":\"25 1\",\"pages\":\"306\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-09-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416008/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Bioinformatics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s12859-024-05923-2\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Bioinformatics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12859-024-05923-2","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Turbocharging protein binding site prediction with geometric attention, inter-resolution transfer learning, and homology-based augmentation.
Background: Locating small molecule binding sites in target proteins, in the resolution of either pocket or residue, is critical in many drug-discovery scenarios. Since it is not always easy to find such binding sites using conventional methods, different deep learning methods to predict binding sites out of protein structures have been developed in recent years. The existing deep learning based methods have several limitations, including (1) the inefficiency of the CNN-only architecture, (2) loss of information due to excessive post-processing, and (3) the under-utilization of available data sources.
Methods: We present a new model architecture and training method that resolves the aforementioned problems. First, by layering geometric self-attention units on top of residue-level 3D CNN outputs, our model overcomes the problems of CNN-only architectures. Second, by configuring the fundamental units of computation as residues and pockets instead of voxels, our method reduced the information loss from post-processing. Lastly, by employing inter-resolution transfer learning and homology-based augmentation, our method maximizes the utilization of available data sources to a significant extent.
Results: The proposed method significantly outperformed all state-of-the-art baselines regarding both resolutions-pocket and residue. An ablation study demonstrated the indispensability of our proposed architecture, as well as transfer learning and homology-based augmentation, for achieving optimal performance. We further scrutinized our model's performance through a case study involving human serum albumin, which demonstrated our model's superior capability in identifying multiple binding sites of the protein, outperforming the existing methods.
Conclusions: We believe that our contribution to the literature is twofold. Firstly, we introduce a novel computational method for binding site prediction with practical applications, substantiated by its strong performance across diverse benchmarks and case studies. Secondly, the innovative aspects in our method- specifically, the design of the model architecture, inter-resolution transfer learning, and homology-based augmentation-would serve as useful components for future work.
期刊介绍:
BMC Bioinformatics is an open access, peer-reviewed journal that considers articles on all aspects of the development, testing and novel application of computational and statistical methods for the modeling and analysis of all kinds of biological data, as well as other areas of computational biology.
BMC Bioinformatics is part of the BMC series which publishes subject-specific journals focused on the needs of individual research communities across all areas of biology and medicine. We offer an efficient, fair and friendly peer review service, and are committed to publishing all sound science, provided that there is some advance in knowledge presented by the work.