Photophysical, thermodynamic and molecular docking studies on the comparative binding interaction of biosynthesized silver nanoparticles with homologous serum proteins: a comprehensive analysis of the interaction mechanisms at both the molecular and

The comprehensive and systematic study of nanoparticle-protein interactions, including the formation of protein corona, is essential for the rational design and safe implementation of nanomaterials in various biomedical and environmental applications as well as to understand the biological fate and behaviour of nanoparticles, especially those produced from natural resources such as plant, fruit and flower extracts. With growing interest among researchers in biosynthesized and eco-friendly nanoparticles, studying their interactions with protein molecules opens new pathways for sustainable nanotechnology with reduced side effects. These interactions can notably affect several nanoparticle properties such as cellular uptake, biodistribution, toxicity, and overall bio-reactivity, and this helps in the rational design of surface-functionalized nanoparticles with tailored properties for specific biomedical functions, such as targeted drug delivery or biosensing. In this paper, we carried out a comprehensive investigation regarding the interaction between the biosynthesized silver nanoparticles (AgNPs) obtained from a plant extract and model transport proteins, namely, bovine serum albumin (BSA) and human serum albumin (HSA), by exploiting multi-spectroscopic and imaging techniques along with theoretical computer-based modeling and simulation studies to explore their binding aspect on the nanosurface, to quantify the strength of interaction and to find the major driving forces involved in these interactions, including an overall understanding of the whole mechanism, and an understanding of the role of secondary structure of the proteins in governing the interaction with AgNPs produced from plant extracts biochemically. Furthermore, a nano surface energy transfer (NSET)-based quenching mechanism being responsible for the quenching of the intrinsic fluorescence of BSA and HSA proteins upon interaction with biosynthesized AgNPs has been proposed. Unlike conventional Förster resonance energy transfer (FRET), NSET offers a more suitable model for nanoparticle-based quenching due to its dependence on nanoparticle surface energy characteristics. Suitable theoretical modeling and simulation studies backed by experimental findings highlight the formation of structural motifs to generate molecular pockets that can hold the nanostructures through interactions between active sites. A clear understanding of nanoparticle-protein interaction through this study will play a crucial role in developing cutting-edge fields like nanomedicine, drug delivery, and biotechnology.