Pre-Training on Large-Scale Generated Docking Conformations with HelixDock to Unlock the Potential of Protein-ligand Structure Prediction Models
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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Preprint |
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2023
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| _version_ | 1866914805734965248 |
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| author | Liu, Lihang Zhang, Shanzhuo He, Donglong Ye, Xianbin Zhou, Jingbo Zhang, Xiaonan Jiang, Yaoyao Diao, Weiming Yin, Hang Chai, Hua Wang, Fan He, Jingzhou Zheng, Liang Li, Yonghui Fang, Xiaomin |
| author_facet | Liu, Lihang Zhang, Shanzhuo He, Donglong Ye, Xianbin Zhou, Jingbo Zhang, Xiaonan Jiang, Yaoyao Diao, Weiming Yin, Hang Chai, Hua Wang, Fan He, Jingzhou Zheng, Liang Li, Yonghui Fang, Xiaomin |
| contents | Protein-ligand structure prediction is an essential task in drug discovery, predicting the binding interactions between small molecules (ligands) and target proteins (receptors). Recent advances have incorporated deep learning techniques to improve the accuracy of protein-ligand structure prediction. Nevertheless, the experimental validation of docking conformations remains costly, it raises concerns regarding the generalizability of these deep learning-based methods due to the limited training data. In this work, we show that by pre-training on a large-scale docking conformation generated by traditional physics-based docking tools and then fine-tuning with a limited set of experimentally validated receptor-ligand complexes, we can obtain a protein-ligand structure prediction model with outstanding performance. Specifically, this process involved the generation of 100 million docking conformations for protein-ligand pairings, an endeavor consuming roughly 1 million CPU core days. The proposed model, HelixDock, aims to acquire the physical knowledge encapsulated by the physics-based docking tools during the pre-training phase. HelixDock has been rigorously benchmarked against both physics-based and deep learning-based baselines, demonstrating its exceptional precision and robust transferability in predicting binding confirmation. In addition, our investigation reveals the scaling laws governing pre-trained protein-ligand structure prediction models, indicating a consistent enhancement in performance with increases in model parameters and the volume of pre-training data. Moreover, we applied HelixDock to several drug discovery-related tasks to validate its practical utility. HelixDock demonstrates outstanding capabilities on both cross-docking and structure-based virtual screening benchmarks. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2310_13913 |
| institution | arXiv |
| publishDate | 2023 |
| record_format | arxiv |
| spellingShingle | Pre-Training on Large-Scale Generated Docking Conformations with HelixDock to Unlock the Potential of Protein-ligand Structure Prediction Models Liu, Lihang Zhang, Shanzhuo He, Donglong Ye, Xianbin Zhou, Jingbo Zhang, Xiaonan Jiang, Yaoyao Diao, Weiming Yin, Hang Chai, Hua Wang, Fan He, Jingzhou Zheng, Liang Li, Yonghui Fang, Xiaomin Machine Learning Computational Engineering, Finance, and Science Biomolecules Protein-ligand structure prediction is an essential task in drug discovery, predicting the binding interactions between small molecules (ligands) and target proteins (receptors). Recent advances have incorporated deep learning techniques to improve the accuracy of protein-ligand structure prediction. Nevertheless, the experimental validation of docking conformations remains costly, it raises concerns regarding the generalizability of these deep learning-based methods due to the limited training data. In this work, we show that by pre-training on a large-scale docking conformation generated by traditional physics-based docking tools and then fine-tuning with a limited set of experimentally validated receptor-ligand complexes, we can obtain a protein-ligand structure prediction model with outstanding performance. Specifically, this process involved the generation of 100 million docking conformations for protein-ligand pairings, an endeavor consuming roughly 1 million CPU core days. The proposed model, HelixDock, aims to acquire the physical knowledge encapsulated by the physics-based docking tools during the pre-training phase. HelixDock has been rigorously benchmarked against both physics-based and deep learning-based baselines, demonstrating its exceptional precision and robust transferability in predicting binding confirmation. In addition, our investigation reveals the scaling laws governing pre-trained protein-ligand structure prediction models, indicating a consistent enhancement in performance with increases in model parameters and the volume of pre-training data. Moreover, we applied HelixDock to several drug discovery-related tasks to validate its practical utility. HelixDock demonstrates outstanding capabilities on both cross-docking and structure-based virtual screening benchmarks. |
| title | Pre-Training on Large-Scale Generated Docking Conformations with HelixDock to Unlock the Potential of Protein-ligand Structure Prediction Models |
| topic | Machine Learning Computational Engineering, Finance, and Science Biomolecules |
| url | https://arxiv.org/abs/2310.13913 |