Adsorption of charged protein residues on an inorganic nanosheet: Computer simulation of LDH interaction with ion channel

Abstract

Abstract. Quasi-two-dimensional and hybrid nanomaterials based on layered double hydroxides (LDH), cationic clays, layered oxyhydroxides and hydroxides of metals possess large specific surface area and strong electrostatic properties with permanent or pH-dependent electric charge. Such nanomaterials may impact cellular electrostatics, changing the ion balance, pH and membrane potential. Selective ion adsorption/exchange may alter the transmembrane electrochemical gradient, disrupting potential-dependent cellular processes. Cellular proteins as a rule have charged residues which can be effectively adsorbed on the surface of layered hydroxide based nanomaterials. The aim of this study is to attempt to shed some light on the possibility and mechanisms of protein "adhesion" an LDH nanosheet and to propose a new direction in anticancer medicine, based on physical impact and strong electrostatics. An unbiased molecular dynamics simulation was performed and the combined process free energy estimation (COPFEE) approach was used.

Bio – Inorganic Interfaces: From Simulations to Applications

“…Interactions at bio-inorganic interface between nanomaterial and the fragments of protein may, in principle, disrupt the functioning of this protein. Using the classical and steered molecular dynamics it was shown that the free energy of adsorption of glutamic residues is sufficiently large to bind the entire protein loop, carrying these residues, with the metal hydroxide nanosheet [12]. Such an interaction may cause the deformation of the protein structure, inhibiting its functioning.…”

Adhesion Effects Within the Hard Matter – Soft Matter Interface: Molecular Dynamics

“…In the present study of interaction effects within the HSI region, the combined process free energy estimation (COPFEE) procedure [34] was utilized, which is based on the potential of mean force (PMF) analysis [35] for constant velocity steered MD. The central idea of the COPFEE approach is a combination of two oppositely directed processes, which allows us to reduce the dependence on the velocity of the pulling procedure and to estimate the level of irreversible energy dissipation in comparison with the free energy change.…”

“…Thus, there are three unknown variables in the system (3b) and only 2 equations. To overcome this problem, the following assumption can be made [34]: if the pulling velocities in both forward and reverse processes are equal and sufficiently small, the entropy generation in both processes should also be approximately equal:…”

“…Thus, the free energy of adsorption can be simply estimated as minus the arithmetic mean of the absolute values of the external work for the forward and reverse processes [34]:…”

“…Free energy of adsorption of anionic molecules on an LDH nanosheet was considered in the previous section as well as in other works [33,34]. The behavior of cationic amino acid residues such as arginine (ARG), lysine and protonated histidine at a cationic nanosheet is also an important question since these also are typical building blocks of proteins and polypeptides, and the possibility of adsorption is not obvious due to electrostatic repulsion.…”