Protein-surface interactions at the nanoscale: Atomistic simulations with implicit solvent models

Abstract

A full molecular-level understanding of protein adsorption in important situations such as the formation of protein films at solid/liquid interfaces or the formation of a protein corona over inorganic nanoparticles is still lacking. All-atomic implicit solvent molecular dynamics (MD) simulations, which are successfully employed in many related protein studies (such as protein folding for example) are emerging also as a useful tool to investigate proteins at surfaces. Implicit solvent simulations replace the detailed description of the solvent by a continuum media and effective atom-atom interactions retaining the atomistic detail in the description of the system of interest. This allows the simulation of larger systems and longer time scales as compared with full MD simulations including explicit solvent. In this brief review, we present an overview of the current state of the application of this technique to the study of problems such as the interaction of proteins with solid surfaces and the structure of protein corona over inorganic nanoparticles. Limitations of the approach and future perspectives are also outlined.

Insights into Preformed Human Serum Albumin Corona on Iron Oxide Nanoparticles: Structure, Effect of Particle Size, Impact on MRI Efficiency, and Metabolization

“…A review of the method can be found in ref. 26 All MD simulations were performed by using the NAMD 2.12 software. 46 In these simulations the Newton equations of motion were solved numerically with a time-step of 2 fs.…”

“…The systems MD3 and MD6 were further simulated for ~12,000,000 steps (note that due to the use of implicit solvent, the kinetics of the simulation cannot be easily related to real, physical time. 26 In the case of the NP with 9 nm of diameter (simulation MD9), this method proved to be computationally very expensive, so we employed an alternative approach. We generated an initial configuration of pre-adsorbed proteins using the program packmol.…”

“…24,25 Moreover, atomistic simulation methodologies are currently being developed able to predict the structure of preformed protein corona for those proteins with known structures. 26,27 To establish general protocols on preforming protein coronas onto particles of different sizes or compositions it is crucial to have good modelling tools to simulate these hybrid nanoconjugates as well as experimental protocols to monitor the quality of the preformed corona, its reproducibility, time stability and impact on the sought-after biomedical uses. To this end, SPIONs have been used here as a model system.…”

Deposition of Polymer Particles with Fibrinogen Corona at Abiotic Surfaces under Flow Conditions

“…where N i is the number of molecules in the interaction zone. Finally, the probability density of fibrinogen molecule adsorption at a given point at the interface was calculated from the Boltzmann formula: ρ p v = e −φ a /kT (7) Using this algorithm, three various adsorption regimes were efficiently modeled (see Supporting Information): (i) the exclusively side-on regime, (ii) the end-on regime, and (iii) the mixed regime where the molecules can adsorb in the end-on orientation if there is not enough space for the side-on orientation. The most relevant quantities derived from the modeling were the numbers of adsorbed fibrinogen molecules forming the corona in the side-on N p and the end-on N p⊥ orientations [9].…”

“…[1][2][3][4]. In the case of nanoparticle carriers, a controlled protein attachment leads to the "corona" formation extensively studied for single-molecule systems and for mixtures comprising the blood serum [5][6][7][8]. However, because of relatively low stability, nanoparticles decorated by coronas are difficult to study by conventional techniques, which require suspension centrifugation or filtration.…”