Low-Resolution Models for the Interaction Dynamics of Coated Gold Nanoparticles with β2-microglobulin

Abstract

A large number of low-resolution models have been proposed in the last decades to reduce the computational cost of molecular dynamics simulations for bio-nano systems, such as those involving the interactions of proteins with functionalized nanoparticles (NPs). For the proteins, “minimalist” models at the one-bead-per residue (Cα-based) level and with implicit solvent are well established. For the gold NPs, widely explored for biotechnological applications, mesoscale (MS) models treating the NP core with a single spheroidal object are commonly proposed. In this representation, the surface details (coating, roughness, etc.) are lost. These, however, and the specificity of the functionalization, have been shown to have fundamental roles for the interaction with proteins. We presented a mixed-resolution coarse-grained (CG) model for gold NPs in which the surface chemistry is reintroduced as superficial smaller beads. We compared molecular dynamics simulations of the amyloid β2-microglobulin represented at the minimalist level interacting with NPs represented with this model or at the MS level. Our finding highlights the importance of describing the surface of the NP at a finer level as the chemical-physical properties of the surface of the NP are crucial to correctly understand the protein-nanoparticle association.

Disclosing the Interaction of Gold Nanoparticles with Aβ(1–40) Monomers through Replica Exchange Molecular Dynamics Simulations

“…A similar behavior was previously observed in the recognition step of the interaction between monolayer-capped AuNPs, where positively charged amino acids R5 and H6 grab the negatively charged tails of the capping-ligands, driving the adsorption of AuNP [16]. The role of the electrostatic interactions is identified as being one of the driving forces for protein-nanoparticle interactions, although the repulsive or attractive nature of the interaction depends both on the covering of the NP and on the primary, secondary, and tertiary structures of the protein [24][25][26][27][28]. A detailed view of a representative binding mode is given in Figure 2b, where the interactions between the K28, H13, H14, and K16 amino acid residues of the Aβ(1-40) and the adsorbed citrates obtained for the MD simulations of the 1:1 Aβ(1-40)/AuNP ratio are highlighted.…”

Orientation of immobilized antigens on common surfaces by a simple computational model: Exposition of SARS-CoV-2 Spike protein RBD epitopes

“…It is a rather common immobilization protocol, because of its simplicity. The interaction is here represented only through a simple Lennard-Jones (LJ) potential, the parameters of which have been defined according to the hydrophobicity index (table S2) [ [33] , [34] , [35] , [36] ]. The most probable orientation (5‰ relative population) is shown in Fig.…”

“…The non-bonded interaction of a residue of type i is represented with a Lennard-Jones (LJ) potential: [ 12 , 13 ]. where r is the nearest distance between the residue and the surface, ε i is the energy at the minimum position, σ i is the equivalent van der Waals radius of each residue and δ i is a size parameter taken from the literature (see tables S2-S7, parameters are taken from [ 14 , 16 , 18 , [33] , [34] , [35] , [36] , [37] ], as indicated in the table captions).…”

“…LJ parameters for epoxide-glyoxyl functionalization is assumed to be equal to SAM-CO 2 H, whereas for gold the parameters have been adapted from reference [ 36 ].…”

Molecular Dynamics Simulations of a Catalytic Multivalent Peptide–Nanoparticle Complex

“…MD simulations at all-atom to coarse-grained scales are assessed tools for the study of non-static binding partners such as that involving a peptide (or protein) and a NP [ 55 , 56 , 57 , 58 ]. The difficulty in identifying the preferred orientation of biomolecules toward a given NP using MD simulations is due to the existence of many putative binding poses on the NP, nearly degenerate in energy, associated to the quite uniformity of the NP.…”