Ultra-small Spherical Gold Nanoparticle Interaction with Fibrinogen: A computational approach

Nanotechnology has an outstanding contribution in numerous fields, and thus it has led to considerable progress. Particularly, in biomedicine, nanoparticles are manipulated in diagnosis, and treatment, specifically in drug delivery. However, novel nanoparticles are recently manipulated widely without estimating their possible risks on health. Especially in intravenous administration of the nanoparticle, where their first contact is with blood components, which can produce potentially harmful effects, especially for plasma proteins. So, the development of more hemo-compatible nanoparticles is necessary. Gold nanoparticles (GNPs) possess outstanding properties, such as simple synthesis, manageable size and shape, and excellent bio-compatibility. Consequently, GNPs have extensively been used in biomedicine, as cancer treatment, bio-catalysis, bio-imaging, and in drug delivery systems. So, the wide range of their applications may lead to possible risks environmentally, as well as on public health. Therefore, it is important to assess their expected toxicity, which in turn has an impact on their therapeutic efficiency. So, in this study we have conducted atomistic level molecular dynamics simulation (MD), to study the effect of an ultra-small (1.5 nm in radius) spherical gold nanoparticle on C-terminal domain of fibrinogen protein’s gamma chain, which is crucial in the blood clotting process and is accomplished via calcium ions located in fibrinogen protein surface at distinct binding sites. So, the calcium ion present in this domain was included in the MD system. Structural analysis represented by Root-Mean-Square of Deviations (RMSDs), Radius- of-Gyration (Rg), Root-Mean-Square of Fluctuations (RMSFs), Solvent-Accessible Surface-Area (SASA), and the total secondary structure content, indicate that there is no substantial change in conformation of the protein. To probe GNP effect on calcium ion’s binding to the protein, the free energy of their binding was calculated, and represented in terms of energy components and the energy contribution of individual protein’s amino acids located within active-site region. Based on the free energy results, there is no detectable change in the binding upon the introduction of GNP. Structural stability is reflected on the stability of the distribution of the charge on the protein surface and was expressed in terms of electrostatic potential surface. So, Ultra-small GNP of radius 1.5 nm is suitable candidate for biomedical applications, since it has no effect on the protein functionality.