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Enhanced compound-protein binding affinity prediction by representing protein multimodal information via a coevolutionary strategy

2022-03-30 · Binjie Guo, Hanyu Zheng, Haohan Jiang, Xiaodan Li, Naiyu Guan, Yanming Zuo, YiCheng Zhang, Hengfu Yang, Xuhua Wang

Due to the lack of a method to efficiently represent the multimodal information of a protein, including its structure and sequence information, predicting compound-protein binding affinity (CPA) still suffers from low accuracy when applying machine learning methods. To overcome this limitation, in a novel end-to-end architecture (named FeatNN), we develop a coevolutionary strategy to jointly represent the structure and sequence features of proteins and ultimately optimize the mathematical models for predicting CPA. Furthermore, from the perspective of data-driven approach, we proposed a rational method that can utilize both high- and low-quality databases to optimize the accuracy and generalization ability of FeatNN in CPA prediction tasks. Notably, we visually interpret the feature interaction process between sequence and structure in the rationally designed architecture. As a result, FeatNN considerably outperforms the state-of-the-art (SOTA) baseline in virtual drug screening tasks, indicating the feasibility of this approach for practical use. FeatNN provides an outstanding method for higher CPA prediction accuracy and better generalization ability by efficiently representing multimodal information of proteins via a coevolutionary strategy.

📄 PDF Abstract BibTeX arXiv:2204.12586

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