Like-charged protein-polyelectrolyte complexation driven by charge patches

Abstract

We study the pair complexation of a single, highly charged polyelectrolyte (PE) chain (of 25 or 50 monomers) with like-charged patchy protein models (CPPMs) by means of implicit-solvent, explicit-salt Langevin dynamics computer simulations. Our previously introduced set of CPPMs embraces well-defined zero-, one-, and two-patched spherical globules each of the same net charge and (nanometer) size with mono- and multipole moments comparable to those of globular proteins with similar size. We observe large binding affinities between the CPPM and the like-charged PE in the tens of the thermal energy, kBT, that are favored by decreasing salt concentration and increasing charge of the patch(es). Our systematic analysis shows a clear correlation between the distance-resolved potentials of mean force, the number of ions released from the PE, and CPPM orientation effects. In particular, we find a novel two-site binding behavior for PEs in the case of two-patched CPPMs, where intermediate metastable complex structures are formed. In order to describe the salt-dependence of the binding affinity for mainly dipolar (one-patched) CPPMs, we introduce a combined counterion-release/Debye-Hückel model that quantitatively captures the essential physics of electrostatic complexation in our systems.

Potential of mean force and transient states in polyelectrolyte pair complexation

“…We finally note that the discontinuity observed in the PE-PE association process may also emerge during the complexation of PEs and globular proteins as indicated in recent coarse-grained computer simulations of more [39] or less [38] resolved protein models with heterogeneous charge distributions. In these cases, counterion-release effects after PE binding to protein surface charge patches have also been identified as the main non-specific interaction responsible for the PE-protein complexation.…”

“…Similar values of r 0 can be estimated from an inspection of the radial distribution of counterions (not shown) around the PE beads (see, e.g., Refs. [38,39,53]). …”

“…The density of the bound ions [38,39] is defined by the number of condensed counterions N and their occupied volume V , i.e., c b = N/V . The condensed counterions reside around each rod at a radial distance between the inner radius σ LJ and the outer radius r 0 .…”

Limiting the valence: advancements and new perspectives on patchy colloids, soft functionalized nanoparticles and biomolecules

“…As pointed out in Section 2.1, this class of proteins is related to charged patchy colloids, and several models are being developed in this respect. 100,103 The appropriate modeling of directional interactions caused by charge inhomogeneities can be challenging, in particular with respect to specific ion effects: for instance, by forming salt bridges, multivalent ions have very drastic effects on the effective interactions between proteins in solution to the point of rendering directional charge repulsions attractive. 116 More refined models which take into account electric multipoles as well as the distribution of charged, neutral and hydrophobic residues have been developed.…”

“…97 A different modeling of charged Janus colloids was proposed to investigate the relation between the order of the multipolar expansion of the inter-particle potential and the resulting minimum-energy clusters. 98 In the context of globular proteins, a set of charged patchy particle models was introduced 99 to study the adsorption of such units on a polyelectrolyte chain 100 or on a polyelectrolyte brush layer. 101 These charged patchy models 99 have also been used to investigate the effect of multivalent electrolytes on the orientational correlations between the patchy units: it was shown that a careful choice of electrolytes could be used to steer the particle assembly.…”