Role of Charge Regulation and Fluctuations in the Conformational and Mechanical Properties of Weak Flexible Polyelectrolytes

Abstract

This work addresses the role of charge regulation (CR) and the associated fluctuations in the conformational and mechanical properties of weak polyelectrolytes. Due to CR, changes in the pH-value modifies the average macromolecular charge and conformational equilibria. A second effect is that, for a given average charge per site, fluctuations can alter the intensity of the interactions by means of correlation between binding sites. We investigate both effects by means of Monte Carlo simulations at constant pH-value, so that the charge is a fluctuating quantity. Once the average charge per site is available, we turn off the fluctuations by assigning the same average charge to every site. A constant charge MC simulation is then performed. We make use of a model which accounts for the main fundamental aspects of a linear flexible polyelectrolyte that is, proton binding, angle internal rotation, bond stretching and bending. Steric excluded volume and differentiated treatment for short-range and long-range interactions are also included. This model can be regarded as a kind of “minimal” in the sense that it contains a minimum number of parameters but still preserving the atomistic detail. It is shown that, if fluctuations are activated, gauche state bond probabilities increase and the persistence length decreases, so that the polymer becomes more folded. Macromolecular stretching is also analyzed in presence of CR (the charge depends on the applied force) and without CR (the charge is fixed to the value at zero force). The analysis of the low force scaling behavior concludes that Pincus exponent becomes pH-dependent. Both, with and without CR, a transition from 1/2 at high pH-values (phantom chain) to 3/5 at low pH-values (Pincus regime) is observed. Finally, the intermediate force stretching regime is investigated. It is found that CR induces a moderate influence in the force-extension curves and persistence length (which in this force regime becomes force-dependent). It is thus concluded that the effect of CR on the stretching curves is mainly due to the changes in the average charge at zero force. It is also found that, for the cases studied, the effect of steric excluded volume is almost irrelevant compared to electrostatic interactions.

Role of pKA in Charge Regulation and Conformation of Various Peptide Sequences

“…Molecular simulations using coarse-grained models have been previously applied to study charge regulation in synthetic weak polyelectrolyte homopolymers, consisting of weak acid or weak base groups [ 8 ]. From these simulations we have learned that ionisation of weak polyelectrolytes increases upon an increase in pH but it is suppressed as compared to the ideal case, as a consequence of electrostatic repulsion between like-charged groups [ 8 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. This increase of ionisation is accompanied by expansion of the polyelectrolyte chain, resulting in a dramatic increase of the end-to-end distance or gyration radius.…”

Effect of pH on the Supramolecular Structure of Helicobacter pylori Urease by Molecular Dynamics Simulations

“…The SGCMC procedure used to obtain the urease charge distribution seems to be an efficient method to generate different charge states to simulate proteins under a wide range of pH conditions [ 16 , 17 , 18 , 19 ]. This procedure assigns charges to monomers of the protein that are not identical but are statistically compatible with the simulated pH.…”

“…We have designed a homemade c program to calculate the different protonation states of Asp, Glu, Arg, Lys and His residues, and the C- and N- termini for seven pHs (2, 3, 4, 5, 6, 7 and 7.5) using the semi-grand canonical Monte Carlo (SGCMC) ensemble [ 16 , 17 , 18 , 19 , 21 ]. A characteristic feature of semi-grand canonical Monte Carlo (SGCMC) simulations is that the total charge is not constant but it fluctuates as a natural result of the dynamic proton binding/unbinding.…”

“…However, the effect of pH on the mechanism of urease is still not known. For this reason, in this work we determined the different protonation states at seven pHs by semi-grand canonical Monte Carlo (SGCMC) [ 16 , 17 , 18 , 19 ] and the behavior of each system through molecular dynamic simulations.…”

Theoretical Modeling of Chemical Equilibrium in Weak Polyelectrolyte Layers on Curved Nanosystems

“…There is quite an abundant body of theoretical work on weak PE in aqueous solutions, focusing on the interplay between charge regulation and fluctuations in the conformational properties. For this topic, molecular simulations are very well suited, as they can provide direct insights and molecular detail on the behavior of the chains in different conditions, and several studies employing hybrid or coupled MD and MC schemes have been performed in the last couple of years in this direction [ 68 , 79 , 80 , 81 , 82 , 83 , 84 ].…”