Bioinformatics Analysis of Wheat Germ Agglutinin (WGA) Interaction with ALDH18A1 in Pediatric Gastrointestinal Cancer Associated with Encephalopathy Symptoms

Abstract

Background: Pediatric gastrointestinal cancers, though rare, are aggressive and may cause neurological symptoms. Aldehyde dehydrogenase 18 family member A1 (ALDH18A1), a key metabolic enzyme, and plant-derived wheat germ agglutinin (WGA), which inhibits cancer growth, were studied. Objectives: The present study aimed to analyze their potential interaction using bioinformatics, exploring structural and biological impacts in pediatric gastrointestinal cancers with neurological involvement. Methods: The amino acid sequences of WGA (Triticum aestivum) and human ALDH18A1 were retrieved from the UniProt database. The three-dimensional structural models were generated using SWISS-MODEL, and model quality was evaluated using tools such as the Ramachandran plot and QMEAN scoring system. Subsequently, ClusPro was employed for protein-protein docking simulations to assess binding energy, hydrogen bonding, and the structural stability of the resulting complexes. Results: Basic local alignment search tool for proteins (BLASTp) analysis showed no significant sequence similarity between WGA and ALDH18A1. Nevertheless, structural modeling confirmed a high-quality model for WGA (QMEAN: +3.54; QMEANDisCo: 0.93) and an acceptable model for ALDH18A1. Molecular docking simulations yielded 28 interaction models, among which Cluster 21 exhibited the lowest binding energy (-1162.7 kcal/mol), indicating the most stable complex. The consistently low binding energies across multiple clusters strongly suggest a significant spatial interaction potential between the two proteins. Conclusions: Although no meaningful sequence homology exists between WGA and ALDH18A1, docking simulations revealed the possibility of a stable structural interaction. This interaction may have a regulatory effect on oxidative stress pathways, cellular survival, and neurological symptoms related to gastrointestinal cancers. The findings provide a foundational framework for future experimental studies aimed at developing plant lectin-based targeted therapies.