Colorectal cancer (CRC) remains a major global health challenge, with chronic inflammation and disruption of epithelial polarity identified as key drivers of tumor progression. Polarity complexes such as Scribble–Mutated in Colorectal Cancer (MCC) are central to maintaining epithelial homeostasis, and their dysregulation has been linked to oncogenic transformation. Drug repurposing offers a promising strategy to accelerate therapeutic discovery by identifying new applications for clinically approved agents. In this study, we investigated abrocitinib (ABR), a selective JAK1 inhibitor, as a candidate for repurposing in CRC. Density functional theory (DFT) calculations at the PBE0-D3/6-31G(d) level were used to examine its electronic properties, including geometry optimization, natural bond orbital (NBO) analysis, molecular electrostatic potential (MESP) mapping, and Fukui function analysis. ABR exhibited a moderate HOMO–LUMO gap (1.827 eV) and an electrophilicity index of 3.492 eV, consistent with favorable reactivity and stability. Molecular docking with the Scribble PDZ1 domain (PDB ID: 6MTV) predicted a strong binding affinity (MolDock score − 78.66 kcal/mol; rerank score − 55.69 kcal/mol), supported by electrostatic and hydrophobic interactions. Importantly, comparative docking with fluorouracil and capecitabine demonstrated that ABR achieved more favorable binding energies and greater interaction stability than these reference CRC drugs, highlighting its superior potential to disrupt Scribble–MCC interactions. Monte Carlo simulations and normal mode analysis further confirmed the dynamic stability of the ABR–PDZ1 complex. Collectively, these findings provide preliminary evidence that abrocitinib may act as a promising modulator of polarity-regulating protein–protein interactions in CRC. While experimental validation remains necessary, this study establishes a computational framework that supports further biochemical and cellular investigations into abrocitinib’s potential as a repurposed therapeutic candidate.

In this study, we investigated the catalytic potential of silicon-based nanoclusters, specifically Si ₆₀ , for hydrogen evolution reactions (HER), focusing on enhancements via substitutional doping with nickel (Ni) and boron (B), where boron and nickel are incorporated into the Si₅₉ lattice, enabling electronic structure modulation. Using Density Functional Theory (DFT) with the B3LYP functional, we examined hydrogen adsorption behavior on boron- doped, Ni-doped, gold-encapsulated Si₅₉ nanoclusters, denoted as B _x ^dop Ni ^dop Au ^enc Si₅₉ (x = 1, 2, 3). Our findings show that doping introduces minimal structural distortion while improving cluster stability and reactivity. Boron-doping notably reduces the energy gap, enhancing electron transfer and promoting hydrogen adsorption. Gibbs free energy analyses confirm somewhat favorable catalytic activity, with ΔG _H values ranging from − 0.837 to − 0.848 eV, highlighting the B _x ^dop Ni ^dop Au ^enc Si₅₉ engineered doped nanoclusters as promising catalysts. Additionally, machine learning models, particularly ElasticNet Regression (R ² = 0.9942), accurately predict hydrogen adsorption energies across various surfaces, from pristine H₂@Si₆₀ to B₃- doped systems. This demonstrates the models’ capability to capture structure–property relationships, accelerating catalyst optimization. Computational screening of Si ₅₉ -based nanostructures revealed that H₂@B ₂ ^dop Ni ^dop Au ^enc Si₅₉ exhibits a ΔG _H value of − 0.836 eV, suggesting comparatively balanced hydrogen adsorption and improved HER catalytic potential among the evaluated systems. Overall, the results suggest that precise doping and surface engineering can significantly enhance the electronic, storage, and catalytic properties of silicon nanoclusters, offering valuable insights for the design of efficient HER catalysts in future sustainable energy technologies.