Abstract: A nanoparticle (NP) entering the human body results in the formation of a nano-bio interface in which a variety of proteins play a major role, forming a nanoparticle protein corona (NPC). Recently, studies of the NPC’s biophysical properties have become a major area of research. It is important to understand, characterize and model the biophysical properties and the molecular interactions related to NPCs in biological environments. Understanding these processes should be achieved at a detailed atomic level, however, molecular studies of NPC models are lacking. Here, we report results from a multiscale modelling approach based on atomistic molecular dynamics (MD) conformational studies of proteins that are known to participate in the protein corona around NPs entering the human body. Using several MD-refined protein structures, in conjunction with Markov State Modeling and molecular docking methods, we generate and analyze model homo- and hetero-oligomers occurring at NPCs, their surface biophysical properties (e.g., such as their hydrophobic fraction of the solvent accessible surface area), and their surface charge distributions. As NPs, we use atomistic models of small (i.e., ~4 nm) TiO2 and SiO2 structures. This computational generative method of atomically detailed models of NPC’s allows the efficient calculation of their corresponding biophysical descriptors and, thus, can be useful in future studies of NPC-biomolecular interactions and their possible effects (e.g., risk assessment of nano-toxicity) in specific biological systems.

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