Multiscale Molecular Dynamics Simulation of Multiple Protein Adsorption on Gold Nanoparticles

Abstract

A multiscale molecular dynamics simulation study has been carried out in order to provide in-depth information on the adsorption of hemoglobin, myoglobin, and trypsin over citrate-capped AuNPs of 15 nm diameter. In particular, determinants for single proteins adsorption and simultaneous adsorption of the three types of proteins considered have been studied by Coarse-Grained and Meso-Scale molecular simulations, respectively. The results, discussed in the light of the controversial experimental data reported in the current experimental literature, have provided a detailed description of the (i) recognition process, (ii) number of proteins involved in the early stages of corona formation, (iii) protein competition for AuNP adsorption, (iv) interaction modalities between AuNP and protein binding sites, and (v) protein structural preservation and alteration.

Dispersion state phase diagram of citrate-coated metallic nanoparticles in saline solutions

“…Recent XPS experiments have also ratified a weak coupling between bound citrate molecules and sodium counterions present in electrolytic solutions 20 . Implicitcitrate models have already accomplished semi-quantitative agreement when studying processes like membrane rupture 47 , protein adsorption 48,49 , NP-induced protein denaturation 23 , and synchronized NP internalization 50 . By means of CG-MD simulations, we estimated the ζ-potential of the NPs for all possible combinations of σ and I, following a protocol introduced elsewhere and described in detail in the "Methods" section 51,52 .…”

“…Recent XPS experiments have also ratified a weak coupling between bound citrate molecules and sodium counterions present in electrolytic solutions 20 . Implicit-citrate models have already accomplished semi-quantitative agreement when studying processes like membrane rupture 47 , protein adsorption 48 , 49 , NP-induced protein denaturation 23 , and synchronized NP internalization 50 .

Fig.

…”

Molecular Dynamics Simulations of a Catalytic Multivalent Peptide–Nanoparticle Complex

“…We also identify that the peptide is forming contact primarily via the carbonyl O atom of 1H, the side chain carboxyl oxygens of 4D and 5D and the terminal carboxyl oxygen of the 6D residues. However, there are some ligands (id: 12,26,33,34,35,40) which form strong binding over the entire last 500 ns of the trajectory, possible by forming contacts with multiple residues at the same time (representative cases are in Figure S6a,b) while some of the ligands (3, 21, 56) (Figure S6c,d) form transient weaker binding patch by showing back and forth motion towards peptide spanning a broad distance between 3 to 20 Å over simulation. Next, we probe inter-ligand fluctuations of the ligands belonging to the binding patch for the peptide.…”

“…Details of the interaction between amyloid β fibrils gold nanoparticles functionalized with ligands with different terminal groups [ 32 , 33 , 34 ] have been disclosed through MD simulation. Multiscale MD simulations [ 35 , 36 ] have been applied to unravel protein conformation and driving forces in protein–corona complexes formation. Similarly, coarse-grained MD simulations [ 37 , 38 , 39 ] of plasma proteins interacting with gold nanoparticles have revealed mutual competition among binding affinities, protein concentration dependent adsorption, effects of orientation on induced conformational changes of proteins upon adsorption on NPs.…”

Biocorona‐induced modifications in engineered nanomaterial–cellular interactions impacting biomedical applications

“…Modern computational kinetic models have begun to understand the NP-biomolecule interactions that dictate BC formation R. Li et al, 2013;Sahneh, Scoglio, Monteiro-Riviere, & Riviere, 2015;Tavanti, Pedone, & Menziani, 2019). A number of methods exist for the study of NP-biomolecular interactions, including ultracentrifugation, gel electrophoresis, and mass spectrometry (Tenzer et al, 2011(Tenzer et al, , 2013Tiede, Hassellöv, Breitbarth, Chaudhry, & Boxall, 2009).…”