Protonation-dependent adsorption of polyarginine onto silver nanoparticles

Abstract

Polyarginine (poly-Arg) and arginine-rich peptides have been attracting enormous interest in chemical and cell biology as cell-penetrating peptides capable of direct intracellular penetration. Owing to advances in protein engineering, arginine-rich fragments are often incorporated into multifunctional bioorganic/inorganic core–shell nanoparticles, enabling them the novel unique ability to cross cells and deliver biopharmaceutical cargos. Therefore, understanding the molecular details of the adsorption, packing, and release of poly-Arg onto or from metal nanoparticles is one of the current challenges. In this work, we carry out atomistic molecular dynamics simulations to identify the most favorable location, orientation, and conformation of poly-Arg adsorbed onto a silver nanoparticle (AgNP). Herein, we utilize the constant protonation approach to identify the role of protonation of side chain arginine moieties in the adsorption of poly-Arg to AgNP as a function of pH. The strong adsorption of unprotonated poly-Arg30 onto the quasispherical surface of AgNP with an average diameter of 3.9 nm is primarily governed by multiple interactions of side chain guanidinium (Gdm) moieties, which get stacked and align flat onto the surface. The protonation of the arginine side chain enhances the protein–solvent interactions and promotes the weakening of the protein–nanoparticle binding. The formation of multiple H-bonds between the protonated Arg residues and water molecules favors exposing the charged Gdm+ moieties to the solvent. Protonated poly-Arg30 is found to be partially bound to AgNP due to some weak protein–nanoparticle contacts, maintained by binding of the amide oxygen atoms of the peptide bond. These results suggest that reversible acid–base switching between the arginine protonation states is able to drive the rearrangement of the polyarginine coating around AgNPs, which could be important for a rational design of “intelligent” multifunctional core–shell nanosystems.

pH-Responsive Coating of Silver Nanoparticles with Poly(2-(N,N-dimethylamino)ethyl methacrylate): The Role of Polymer Size and Degree of Protonation

“…61,72,83−86 Recently, such an approach has been applied to simulate pH-responsive conformation dynamics of single-chain oligomers and their self-assembly for poly(acrylic acid) 61,87 and poly(alkyl acrylic acids), 83,84,88−90 poly(ethylenimine), 85 poly(vinylamine), 91 and poly(arginine). 54 To simulate the polymer response to changes in pH, the required value of the degree of protonation (α) was achieved by the attachment of a proton to the nitrogen atom of the tertiary dimethylamino side group, which switches its charge from 0 to +1 (Figures 1b and 2). The degree of protonation α of PDMAEMA is given by eq 2.…”

Quantitative Prediction of pH-Controlled Ionization of Oligopeptides

“…To answer this question, we used two short oligopeptides with weak acid and weak base side-chains as a model system with a complex ionisation response in which acid and base groups mutually influence each other. The importance of coupling charge distribution and conformation in intrinsically disordered proteins has been previously demonstrated in both simulations and experiments, [36][37][38][39] albeit disregarding their ionisation response. Conversely, our model considers the ionisation response of short oligopeptides and its relation to molecular geometry and conformation, presumably for the first time.…”

Biogenic Synthesis and Characterization of Antioxidant and Antimicrobial Silver Nanoparticles Using Flower Extract of Couroupita guianensis Aubl.

“…The system was simulated at 300 K for 100 ns while the Ag atoms positions were kept frozen, as was carried out previously [51][52][53][54]. The Gromos 54a7 force field was employed for the simulation of the adsorption of molecules over the AgNP surface [55][56][57]. The parameters for the molecules were retrieved from the Automated Topology Builder (ATB) [58] and the parameters for the AgNP were obtained from the work of Heinz et al [59].…”