CarsiDock-Cov: A deep learning-guided approach for automated covalent docking and screening.
10.1016/j.apsb.2025.07.043
- Author:
Chao SHEN
1
;
Hongyan DU
2
;
Xujun ZHANG
2
;
Shukai GU
2
;
Heng CAI
3
;
Yu KANG
2
;
Peichen PAN
2
;
Qingwei ZHAO
1
;
Tingjun HOU
1
Author Information
1. Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
2. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
3. Hangzhou Carbonsilicon AI Technology Co., Ltd., Hangzhou 310018, China.
- Publication Type:Journal Article
- Keywords:
Binding pose generation;
Covalent binders;
Covalent bond constraints;
Covalent docking;
Covalent drug design and discovery;
Deep learning;
Non-covalent scoring;
Virtual screening
- From:
Acta Pharmaceutica Sinica B
2025;15(11):5758-5771
- CountryChina
- Language:English
-
Abstract:
The interest in covalent drugs has resurged in recent decades, spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening. Herein, we present CarsiDock-Cov, a new paradigm distinguishing itself as the first deep learning (DL)-guided approach for covalent docking. CarsiDock-Cov retains the core components of its non-covalent predecessor, leveraging a DL model pretrained on millions of docking complexes to predict protein-ligand distance matrices, along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses. Additionally, it incorporates several key enhancements specifically tailored to optimize the protocol for covalent docking applications. Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands, and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor, but also exhibits competitive performance against various state-of-the-art covalent docking tools. Collectively, our approach represents a significant advance in covalent docking methodology, offering an automated and efficient solution that shows considerable promise for accelerating covalent drug discovery and design.
