Hydrophobicity and Electrostatic Properties in Models of Protein Aggregates

A nanoparticle entering the human body results in the formation of a nano-bio interface. This results in a dynamic interaction that takes place amongst the nanoparticle surface and a variety of biomolecules, especially proteins, forming a protein corona (PC). Recently, studies of the nanoparticle protein corona (NP-PC) biophysical properties have become a significant area of research. It is important to understand, characterize and model the biophysical properties and the molecular interactions related to the NP-PC. Protein-nanoparticle interactions are driven largely by corresponding physio-chemical changes. Here, we perform atomistic molecular dynamic (MD) conformational studies of five important proteins that are known to participate in the protein corona around the nanoparticle in the human body: Human Serum Albumin, Apolipoprotein, Human Surfactant Protein D, Alpha-1 antitrypsin, and Mucin 2 D3 domain. Using their structures from the RCSB protein data bank, we perform a statistical analysis of their MD trajectories to determine their representative, average equilibrium structures and their possible outlier structures (i.e., most different from the representative ones). Using these structures in conjunction with docking simulations, we generate both homo-oligomers and hetero-oligomers and analyze their surface biophysical properties such as their hydrophobic fraction of the solvent accessible surface area (SASAH) and surface charges. We also use atomistic models of TiO2 and SiO2 nanoparticles to generate and study the NP-PC interface around these nanoparticles, describe specific residues found in the NP-PC interfaces, and show that accurate SASAH, SASA+, SASA- values, and PC surface charges can be estimated for atomistic models of NP-PCs. The efficient yet accurate characterization of NP-PC biophysical properties should be useful in future studies of NP-NP and NP-biomolecular interactions and their possible effects (e.g., toxicity) in specific biological systems.