Integrating Conformational Sampling and Siamese Learning to Predict Mutation-Induced Binding Affinity Changes in Abelson Tyrosine Kinase and Its Ligands.

Liangxu Xie¹, Teng Ma², Xiaohua Lu¹, Dawei Zhang¹, Lei Xu¹, Mingjun Yang³, Young-Seob Jeong⁴, Shan Chang¹, Xiaojun Xu¹

¹Institute of Bioinformatics and Medical Engineering, Jiangsu University of Technology, Changzhou 213001, China.

²Department of Thyroid Surgery, Weifang People's Hospital, Weifang 261000, China.

³Shenzhen Jingtai Technology Co., Ltd. (XtalPi), Shenzhen 518045, China.

⁴Department of Computer Engineering, Chungbuk National University, Cheongju 28644, South Korea.

PubMed DOI

Abstract

Predicting the impact of mutations on protein-ligand binding affinity is crucial in drug discovery, particularly in addressing drug resistance and repurposing existing drugs. Conventional structure-based methods are often limited by their reliance on static cocrystal structures. To address this, we integrate AlphaFold 2 (AF2) subsampling with a Siamese neural network to predict mutation-induced ch…

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