A multiscale model of protein adsorption on a nanoparticle surface

Abstract

We present a methodology to quantify the essential interactions at the interface between inorganic solid nanoparticles (NPs) and biological molecules. Our model is based on pre-calculation of the repetitive contributions to the interaction from molecular segments, which allows us to efficiently scan a multitude of molecules and rank them by their adsorption affinity. The interaction between the biomolecular fragments and the nanomaterial are evaluated using a systematic coarse-graining scheme starting from all-atom molecular dynamics simulations. The NPs are modelled using a two-layer representation, where the outer layer is parameterized at the atomistic level and the core is treated at the continuum level using Lifshitz theory of dispersion forces. We demonstrate that the scheme reproduces the experimentally observed features of the NP protein coronas. To illustrate the use of the methodology, we compute the adsorption energies for human blood plasma proteins on gold NPs of different sizes as well as the preferred orientation of the molecules upon adsorption. The computed energies can be used for predicting the composition of the NP-protein corona for the corresponding material.

In Silico Prediction of Protein Adsorption Energy on Titanium Dioxide and Gold Nanoparticles

“…The UA method was used to calculate the interaction energy between each protein and a spherical NP. A full theoretical description of the methodology can be found in [ 10 , 19 , 20 ] and all Supplementary Materials for this article are available online. The multiscale modelling performs tiered summation of the pairwise interactions between amino acids of the protein and the nanomaterial, treating each AA as a single bead located at the α-carbon position.…”

“…Here, we calculate binding energies only for spherical NPs defined by their radius R and neglect the electrostatic interaction. We approximate the long-range interaction between an AA bead and the NP through the Hamaker potential obtained by integration over the volumes of the NP and AA bead, where is the radius of the AA bead, calculated as discussed in Appendix B , is the distance between the centre of the AA bead and the centre of the NP, is the Hamaker constant for interaction of the nanomaterial with the AA through water calculated as described in Appendix B and in previous work [ 10 , 21 ], and is the cutoff range for the surface potential of mean force (PMF) [ 10 ]. At short range (i.e., at distances less than ), part of the volume of the NP included in the above expression is already accounted for in the surface potential.…”

“…At short range (i.e., at distances less than ), part of the volume of the NP included in the above expression is already accounted for in the surface potential. We thus correct this expression by subtracting the potential for the lens segment formed by the region of the NP included in the short-range surface potential, resulting in [ 10 ], The total core potential is then obtained by summing over the potential for AA beads present in the protein, , where is the occupancy of the AA bead as extracted from the PDB file. Likewise, the short-range potential is calculated through summation of the short-range PMF for each bead, [ 10 , 20 , 21 ].…”

“…This adsorption free energy can, in principle, be calculated ab initio through molecular dynamics, but at a significant computational cost, which renders it impractical for evaluating many NP-protein pairs. To overcome this, we previously proposed a multiscale method that allows one to compute the adsorption free energy between an NP and a protein with known 3D structure, based on a united-atom (UA) coarse-graining scheme in which each amino acid (AA) is represented by a single bead [ 10 ]. The 3D structure of the folded protein is essential for this calculation as specific characteristics (charged patches or crevasses) on the protein surface can be a significant, if not dominant, component of the interaction.…”

Nanomaterials in the Environment Acquire an “Eco‐Corona” Impacting their Toxicity to Daphnia Magna—a Call for Updating Toxicity Testing Policies

“…As per the well‐known Vroman effect, biomolecules in high abundance may bind initially to be subsequently replaced by molecules with a higher affinity for the NM surface, as shown schematically in Figure ; evolution of the NMs corona in this manner can result from NMs uptake and transport to new locations with different biomolecule availability, or from cellular secretions in response to the NMs presence which can alter the corona composition . Indeed, evolution of the NM (eco)corona is an area of active research, both experimentally and through development of predictive models based on affinities …”