Structural Determinants and Stability of Frutalin Isoforms from Artocarpus incisa: Insights from Molecular Modeling, Docking, and Dynamics Simulations

Resumo

Frutalin (FTL) is a plant lectin derived from the seeds of Artocarpus incisa (breadfruit), previously reported to exhibit diverse biological activities. In this study, we investigated the structural variability among FTL isoforms and the molecular determinants underlying their quaternary stability and ligand interactions. FTL was isolated by affinity chromatography on D-galactose-agarose, and deconvoluted mass spectrometry revealed multiple species around 16 kDa, suggesting the presence of isoforms. Five structural models were generated based on sequences obtained by RT-PCR, using the crystallographic structure as a template. Molecular docking analyses were performed using HEX 8.0.0 to evaluate lectin–carbohydrate interactions, while molecular dynamics simulations were conducted with the GROMACS package to assess the stability of the tetrameric assembly in an aqueous environment. The results indicate that specific residues contribute to the stabilization of the quaternary structure, maintaining inter-subunit hydrogen bonding, whereas structural rigidity is strongly influenced by residues within β-sheet regions. All isoforms exhibited comparable interaction profiles with D-galactose and D-mannose, involving approximately eight key contacts per complex, suggesting conserved binding behavior. These findings indicate that structural variability among isoforms does not significantly alter carbohydrate recognition, highlighting the need for further investigations using larger or more complex ligands. Overall, this study demonstrates the potential of integrated bioinformatics approaches to elucidate structure–function relationships in lectins, contributing to the expansion of their biotechnological applications.

Keywords: Frutalin, Artocarpus incisa lectin, Bioinformatics, Molecular Docking, Molecular Dynamics.