AI-Powered Structural and Co-Expression Analysis of Potato (Solanum tuberosum) StABCG25 Transporters Under Drought: A Combined AlphaFold, WGCNA, and MD Approach

Drought stress significantly impacts potato (<i>Solanum tuberosum</i>) yield and quality, necessitating the identification of molecular regulators involved in stress response. This study presents a systems-level, integrative in silico strategy to characterize <i>StABCG25</i> transporter homologs, key players in abscisic acid (ABA) export in Arabidopsis, to evaluate their potential role in drought adaptation. We performed a genome-wide scan of the potato genome and identified four <i>StABCG25</i> isoforms. A comprehensive computational framework was applied, including transcriptomic profiling, Weighted Gene Co-expression Network Analysis (WGCNA), AlphaFold2-based 3D modeling, docking, and long-timescale Molecular Dynamics (MD) simulations. Expression analyses revealed the coordinated upregulation of <i>StABCG25-2</i> and <i>-4</i> in the drought-tolerant FB clone, contrasted by suppression or instability in sensitive cultivars. WGCNA placed <i>StABCG25-2</i> as a hub gene in ABA-enriched stress response modules, while <i>StABCG25-4</i> was associated with plastid-related pathways, suggesting functional divergence. Structurally, <i>StABCG25-2</i> and -6 exhibited high conformational stability in MD simulations, supported by consistent RMSD/RMSF profiles and MM/PBSA-based binding energy estimates. In contrast, <i>StABCG25-5B</i>, despite favorable docking scores, demonstrated poor dynamic stability and unreliable binding affinity. Overall, this study highlights the critical role of transcriptional coordination and structural robustness in the functional specialization of <i>StABCG25</i> isoforms under drought stress. Our findings underscore the value of combining WGCNA and molecular dynamics simulations to identify structurally and functionally relevant ABA transporters for future crop improvement strategies.