SERS sensing of the biomolecule of Palbociclib (PCB) adsorbed on Au3 cluster: DFT, reactivity, docking and MD simulations

Understanding how anticancer drugs interact with metallic nanoclusters is essential for developing next-generation sensing and delivery platforms. In this study, we investigate the adsorption behavior, spectroscopic response, reactivity, and biological binding characteristics of Palbociclib (PCB) on a gold triatomic cluster (Au3) using an integrated computational framework. Density functional theory (DFT) calculations reveal strong and site-selective adsorption of PCB on Au3 accompanied by pronounced charge transfer and significant modulation of the molecule’s electronic structure including reduced HOMO-LUMO gaps, enhanced polarizability, and improved nonlinear optical (NLO) characteristics. Vibrational and SERS analyses show characteristic red shifts and intensity enhancements, confirming stable coordination through key nitrogen and oxygen bearing functional groups. Solvent-phase calculations further demonstrate that PCB-Au3 complexes gain substantial stabilization in aqueous media, reinforcing their potential in biological environments. Molecular docking and 100 ns molecular dynamics simulations with the 5GS4 protein indicate that both free PCB and PCB-Au3 form thermodynamically favorable and dynamically stable complexes, with PCB-Au3 exhibiting enhanced interaction diversity through hydrophobic, hydrogen-bonding, and Au-induced electronic effects. MM-GBSA analysis supports these findings, revealing competitive binding energies for both ligands. Collectively, these results highlight Au3 nanoclusters as promising nanoscale scaffolds for SERS-based detection and controlled delivery of PCB, providing valuable insights for cancer diagnostic and theranostic applications.