Computational insights into CHST11 and CHST13: homology modeling, molecular docking, and dynamics simulation for novel therapeutic targeting in cancers

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a major global health concern due to its high mortality and resistance to current therapies. Emerging evidence highlights the role of carbohydrate sulfotransferases CHST11 and CHST13 in driving tumor progression, activating MAPK signaling, and mediating chemoresistance. In this study, homology modeling, molecular docking, and molecular dynamics (MD) simulations were used to explore the structural and functional properties of CHST11 and CHST13, key sulfotransferases implicated in HCC. Active site analysis and interaction profiling guided the screening of 60 bioactive compounds, with ascorbic acid as a reference. Capsaicin bound strongly to both CHST11 and CHST13, whereas erlotinib exhibited selective affinity for CHST13. Notably, the CHST13-capsaicin complex demonstrated the most favorable binding energy and structural stability in MD simulations. These findings highlight the distinct dynamic behaviors of both targets and support their potential as druggable proteins in HCC, offering a basis for developing selective therapeutic inhibitors. © 2025