Computational Modelling of Tunicamycin C Interaction with Potential Protein Targets: Perspectives from Inverse Docking with Molecular Dynamic Simulation

Computational Modelling of Tunicamycin C Interaction with Potential Protein Targets: Perspectives from Inverse Docking with Molecular Dynamic Simulation

Protein glycosylation plays a crucial role in cancer biology, influencing essential cellular processes such as cell signalling, immune recognition, and tumour metastasis. Therefore, this study highlights the therapeutic potential of targeting glycosylation in cancer treatment, as modulating these mo...

Full description

Saved in:
Bibliographic Details
Main Authors: Vivash Naidoo, Ikechukwu Achilonu, Sheefa Mirza, Rodney Hull, Jeyalakshmi Kandhavelu, Marushka Soobben, Clement Penny
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Current Issues in Molecular Biology
Subjects:
glycosylation
Tunicamycin
thymidine kinase 1
protein kinase A
molecular dynamics
therapeutic targets
Online Access:https://www.mdpi.com/1467-3045/47/5/339
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Protein glycosylation plays a crucial role in cancer biology, influencing essential cellular processes such as cell signalling, immune recognition, and tumour metastasis. Therefore, this study highlights the therapeutic potential of targeting glycosylation in cancer treatment, as modulating these modifications could disrupt the fundamental mechanisms driving cancer progression and improve therapeutic outcomes. Recently, Tunicamycin C, a well-known glycosylation inhibitor, has shown promise in breast cancer treatment but remains unexplored in colorectal cancer (CRC). Thus, in this study, we aimed to understand the potential action of Tunicamycin C in CRC using in silico studies to identify possible drug targets for Tunicamycin C. First, we identified two target proteins using the HTDocking algorithm followed by GO and KEGG pathway searches: thymidine kinase 1 (TK1) and cAMP-dependent protein kinase catalytic subunit alpha (PKAc). Following this, molecular dynamics modelling revealed that Tunicamycin C binding induced a conformational perturbation in the 3D structures of TK1 and PKAc, inhibiting their activities. This interaction led to a stable design, promoting optimal binding of Tunicamycin C in the hydrophobic pockets of TK1 and PKAc. Serial validation studies highlighted the role of active site residues in binding stabilisation. Tunicamycin C exhibited high binding affinity with TK1 and PKAc. This study provides a way to explore and repurpose novel inhibitors of TK1 and PKAc and identify new therapeutic targets, which may block glycosylation in cancer treatment.
ISSN:1467-3037
1467-3045

Similar Items