Abstract
Understanding the interaction between gold nanostructures and biomolecules is critical for advancing applications in nanomedicine, biosensing, and bioelectronics. Here, we assess the performance of density functional tight binding (DFTB) with Grimme's D3-(BJ) dispersion correction by comparing it to available density functional theory (DFT) results in the literature for gold nanocluster-amino acid complexes. Five clusters (Au(3), Au(8), Au(13), Au(20), Au(32)) interacting with ten amino acids were investigated at both amine and carboxyl binding sites. System selection was guided by the availability of the corresponding DFT results in the literature. DFTB reproduces the qualitative binding preference for amine over carboxyl adsorption, with interaction energies typically within 2-3 kcal/mol of DFT for Au(3) and Au(8). Au-X bond lengths are systematically longer by ∼0.4-0.7 Å, and larger deviations appear for Au(13) and nitrogen-containing cyclic amino acids. For Au(20), good agreement with DFT is obtained for alanine at the amine binding site and tryptophan at both the amine and carboxyl sites, suggesting that DFTB remains reliable beyond the smallest clusters. For Au(32), although a direct comparison is not possible, the data indicate similar binding preferences to those found for smaller clusters. In addition, nitrogen-containing cyclic amino acids (such as histidine, proline, and tryptophan) tend to show larger discrepancies, reflecting the increased importance of polarization, charge redistribution, and multiple competing binding motifs in these systems. As the cluster size increases from Au(3) to Au(32), DFTB generally preserves qualitative trends but exhibits growing quantitative deviations, indicating that transferability toward more metallic, nanoparticle-like regimes must be assessed with caution. Our results demonstrate that DFTB + D3-(BJ) provides an efficient and sufficiently accurate framework for screening Au-biomolecule interactions.