Aditya, M.M.AdityaAdwaith, P.P.AdwaithKrishna, A.A.KrishnaReman, K. S.K. S.RemanPushpavanam, KarthikKarthikPushpavanam2025-11-072025-11-072025-09-0110.1116/6.00047902-s2.0-105020375105http://repository.iitgn.ac.in/handle/IITG2025/33447Peptides that selectively bind to inorganic surfaces play a crucial role in nanobiotechnology, biomaterials, and biosensing applications. While phage display has been the predominant method for identifying such peptides, its selection process is influenced by propagation biases and experimental constraints, which may lead to the exclusion of peptides with superior binding affinity. In this study, we implement a molecular dynamics simulation to systematically assess the binding affinity of 46 solid-binding peptides, which were manually curated from literature with previously identified affinities to various surfaces to Au(111). We perform a comprehensive analysis, including interaction energy calculations, molecular mechanics/Poisson–Boltzmann-surface area, root mean square deviation, and distance of each residue with Au(111) to elucidate the molecular determinants of solid-binding peptide-Au(111) interactions. Our results reveal that while phage display-derived peptides exhibit affinity, several peptides not previously categorized as Au(111) binding show stronger affinity than the experimentally identified Au-binding sequences. We propose the term “promiscuous binding peptides” to describe these sequences, which demonstrate high affinity for surfaces beyond their original selection targets. Our findings highlight the limitations of experimental selection techniques and emphasize the potential of computational screening in identifying higher-affinity peptides toward the target metal interfaces. This study establishes a foundation for advancing the rational design of functional solid-binding peptides.falseArticle155941061 September 20250051010WOS:001606734600002