Zhang Xujun, Jiang Linlong, Weng Gaoqi, Shen Chao, Zhang Odin, Liu Mingquan, Zhang Chen, Gu Shukai, Wang Jike, Wang Xiaorui, Du Hongyan, Zhang Hui, Zhang Ke, Wang Ercheng, Hou Tingjun
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China.
Vollum Institute, Oregon Health and Science University, Portland, OR 97239, United States.
Nucleic Acids Res. 2025 Jul 7;53(W1):W306-W315. doi: 10.1093/nar/gkaf379.
Protein-protein interactions (PPIs) are fundamental to cellular functions, yet predicting and analyzing their 3D structures remains a critical and computationally demanding challenge. To address this, the HawkDock web server was developed as an integrated computational platform for predicting and analyzing protein-protein complexes. Over the past 6 years, HawkDock has successfully processed >234 000 computational tasks. In this study, an updated version of HawkDock was developed with the following advancements: (1) a deep learning-based flexible docking method, GeoDock, has been integrated to improve docking accuracy, particularly for apo-protein structures; (2) the VD-MM/GBSA method, which outperforms conventional MM/GBSA approaches in predicting binding affinities, has been implemented; (3) a new Mutation Analysis Module has been added to systematically evaluate the energetic impacts of amino acid mutations on protein-protein binding; (4) the server has been migrated to a high-performance cluster with Amber upgraded to version 24. Here, we describe the general protocol of HawkDock2, with a particular focus on its new features related to flexible docking, VD-MM/GBSA affinity prediction, and amino acid residue mutations. Comprehensive validation studies have demonstrated the reliability and effectiveness of these new features. HawkDock2 will remain freely accessible to all users at http://cadd.zju.edu.cn/hawkdock/.
蛋白质-蛋白质相互作用（PPIs）是细胞功能的基础，但预测和分析其三维结构仍然是一项关键且计算要求很高的挑战。为了解决这个问题，HawkDock网络服务器被开发为一个用于预测和分析蛋白质-蛋白质复合物的集成计算平台。在过去6年里，HawkDock已成功处理了超过234000个计算任务。在本研究中，开发了HawkDock的更新版本，有以下进展：（1）集成了基于深度学习的柔性对接方法GeoDock，以提高对接准确性，特别是对于无配体蛋白质结构；（2）实施了VD-MM/GBSA方法，该方法在预测结合亲和力方面优于传统的MM/GBSA方法；（3）添加了一个新的突变分析模块，以系统评估氨基酸突变对蛋白质-蛋白质结合的能量影响；（4）服务器已迁移到高性能集群，Amber已升级到24版。在此，我们描述了HawkDock2的一般协议，特别关注其与柔性对接、VD-MM/GBSA亲和力预测和氨基酸残基突变相关的新功能。全面的验证研究证明了这些新功能的可靠性和有效性。所有用户仍可通过http://cadd.zju.edu.cn/hawkdock/免费访问HawkDock2。
