Insights from molecular dynamics into bactericidal mechanisms of copper and carbon substrates using reactive force-field

Reactive Force Field (ReaxFF) molecular dynamics (MD) simulations, which allow dynamic bond formation and charge transfer, were conducted to investigate the incipient bactericidal/bacteriostatic activity of copper (Cu) and carbon (C) surfaces with varying crystallinity. Five materials were modelled including nanocrystalline (NC) and polycrystalline (PC) copper and carbon as well as amorphous carbon (aC), and simulated to assess the effect of grain boundary, crystallinity, and chemistry of the material on the charge transfer mechanisms at the BamABCDE protein–substrate interface within the bacterial outer membrane. The simulation outputs were assessed using charge distribution, potential energy root mean square deviation (RMSD), radius of gyration (Rg), root mean square fluctuation (RMSF), backbone dihedrals, residue displacement, and Ramachandran plot. Copper based substrates, particularly NC Cu, showed faster kinetics of protein destabilisation (strongly bactericidal behaviour), marked by an increased torsional strain and loss of secondary structure. In contrast, carbon substrates, especially aC, preserved structural integrity and maintained stable electrostatic profiles, which suggested a bacteriostatic behaviour. What MD uniquely revealed at the atomic scale was a divergence in attack strategy between copper substrates: NC-Cu induced early and spatially focused backbone collapse through torsional perturbation, while PC-Cu caused widespread residue-level destabilisation through grain-boundary-driven electrostatic disruption. These deformation patterns emerged within picoseconds of interface formation, a timescale and spatial resolution not accessible through experiment, enabling direct visualisation of early protein unfolding, residue-specific displacement, and domain-level instability. These findings provide a pathway to advance atomic-level mechanistic understanding, enabling the purposeful design of highly efficient antibacterial coatings for applications in healthcare, transportation, food and industrial settings. Statement of significance This study provides atomistic evidence of how copper and carbon surfaces differ in their early antibacterial behaviour. Reactive molecular dynamics (ReaxFF) simulations of five substrates (NC-Cu, PC-Cu, NC-C, PC-C and aC) interacting with the BamABCDE protein show that copper, especially nanocrystalline Cu induces rapid backbone torsional strain, elevated RMSD and Rg, and large residue displacements, indicating early-stage unfolding. Carbon surfaces, particularly amorphous carbon, maintain low RMSD and stable φ/ψ conformations. Copper also exhibits strong early charge accumulation (∼0.2 C), whereas carbon remains nearly neutral. These substrate-dependent early perturbations distinguish bactericidal (Cu) from bacteriostatic (C) behaviour and provide mechanistic insight for designing next-generation antimicrobial coatings.