Dopamine-Decorated TiO₂ Nanoparticles in Water: A QM/MM vs an MM Description

Abstract

Nanoparticle functionalization is a modern strategy in nanotechnology to build up devices for several applications. Modeling fully decorated metal oxide nanoparticles of realistic size (few nanometers) in an aqueous environment is a challenging task. In this work, we present a case study relevant for solar-light exploitation and for biomedical applications, i.e., a dopamine-functionalized TiO 2 nanoparticle (1700 atoms) in bulk water, for which we have performed an extensive comparative investigation with both MM and QM/MM approaches of the structural properties and of the conformational dynamics. We have used a combined multiscale protocol for a more efficient exploration of the complex conformational space. On the basis of the results of this study and of some QM and experimental data, we have defined strengths and limitations of the existing force field parameters. Our findings will be useful for an improved modeling and simulation of many other similar hybrid bioinorganic nanosystems in an aqueous environment that are pivotal in a broad range of nanotechnological applications.

Molecular dynamics simulations of cRGD-conjugated PEGylated TiO2 nanoparticles for targeted photodynamic therapy

“…The partial atomic charges and LJ (12,6) parameters for the TiO2 NP were assigned according to the coordination number of titanium and oxygen atoms using an optimized version of the original Matsui-Akaogi FF [49] further refined by Brandt et al [50]. This FF has been tested and validated by one of us for a TiO2 NP model tethered with small organic molecules [51]. Lorentz-Berthelot rules were used to obtain the cross-term parameters for LJ interactions between unlike atoms.…”

Effect of dopamine-functionalization, charge and pH on protein corona formation around TiO2 nanoparticles

“…In the present computational study, we clarify how the surface chemistry of fully-decorated dopamine 2.2 nm TiO 2 NPs (whose structure was obtained in a previous study by some of us through quantum mechanicaldensity functional theorycalculations) [62][63][64][65] affects the protein corona formation with two intracellular proteins, namely PARP1 and HSP90, under explicit water solvation. The NP model and the proteins we consider here are the same as those studied experimentally by Lastra et al 17 Tunable protonation states of the terminal amine group of dopamine (DA) ligands ( pK a ∼9.75) at physiological and alkaline conditions allow a realistic modulation of the NP surface charge, giving rise to a cationic (net charge +46) and a neutral NP (net charge zero) model, respectively.…”

“…This model has been obtained by quantum mechanical calculations, based on density functional theory, in previous works. [62][63][64][65] Here, the relative atomic positions of Ti and O atoms are kept rigid during all the MD simulations, whereas the DA atoms are allowed to move. The charge state of the NP is determined by the protonation state of the DA amino group: at physiological pH conditions (7.4), we consider the DA amino group to be protonated (cationic NP), whereas at alkaline pH conditions (11.5) we consider the DA amino group to be deprotonated (neutral NP).…”

Exploring the drug loading mechanism of photoactive inorganic nanocarriers through molecular dynamics simulations

“…28,29 The force field accuracy for the description of similar systems has been assessed in another previous work by some of us. 26 This is an excellent starting point for our MM investigation on the drug loading capacity of these systems.…”

“…This work benefits from our previous studies, where we have developed chemically stable spherical TiO 2 NP models with high-level quantum mechanical (QM) methods, 22 have explored their water solvation with the QM/MM approach 23 and have also assessed the validity and accuracy of the chosen MM force field parameters used in the present study for the description of bioinorganic nanohybrids against QM and QM/ MM calculations. [24][25][26] Moreover, for both TETT and DOPAC ligands, we have already obtained stable optimized structures of fully decorated TiO 2 NPs by QM calculations, 24,25 which have been an excellent starting point for the MD simulations.…”