Driving forces behind ion-ion correlations.
Explore the source record for details and available documents.
Chemistry↗
Biomedical subjects
Mikael Lund
Publications and source records attributed to Mikael Lund.
On the complexation of proteins and polyelectrolytes.
Both natural and synthetic polyelectrolytes form strong complexes with a variety of proteins. One peculiar phenomenon is that association can take place even when the protein and the polyelectrolyte carry the same charge. This has been interpreted as if the ion-dipole interaction can overcome the repulsive ion-ion interaction. On the basis of Monte Carlo simulations and perturbation theory, we propose a different explanation for the association, namely, charge regulation. We have investigated three different protein-polymer complexes and found that the induced ionization of amino acid residues due to the polyelectrolyte leads to a surprisingly strong attractive interaction between the protein and the polymer. The extra attraction from this charge-induced charge interaction can be several kT and is for the three cases studied here, lysozyme, alpha-lactalbumin, and beta-lactoglobulin, of the same magnitude or stronger than the ion-dipole interaction. The magnitude of the induced charge is governed by a response function, the protein charge capacitance Z2-Z2. This fluctuation term can easily be calculated in a simulation or measured in a titration experiment.
Computer Simulation↗
Enhanced protein adsorption due to charge regulation.
When a protein molecule approaches a charged surface, its protonation state can undergo dramatic changes due to the imposed electric potential. This has a large impact on adsorption strengths that may be enhanced by several kT. Using mesoscopic simulation techniques as well as analytical theories, we have investigated this regulation mechanism and demonstrate how it is influenced by salt concentration and solution pH. Using hisactophilin as a test case, we show how the binding to a lipid membrane is governed by small changes in pH and that this is intimately coupled to the charge regulation mechanism.
Adsorption↗
On the charge regulation of proteins.
It is known that the overall charge of a protein can change as the molecule approaches a charged object like another protein or a cell membrane. We have formalized this mechanism using a statistical mechanical framework and show how this rather overlooked interaction increases the attraction between protein molecules. From the theory, we can identify a unique property, the protein charge capacitance, that contains all information needed to describe the charge regulation mechanism. The capacitance can be obtained from experiment or theory and is a function of pH, salt concentration, and the number of titrating residues. For a range of different protein molecules, we calculate the capacitance and demonstrate how it can be used to quantify the charge regulation interaction. With minimal effort, the derived formulas can be used to improve existing models by including a charge regulation term. Good agreement is found between theory, simulations, and experimental data.
Electric Capacitance↗
A mesoscopic model for protein-protein interactions in solution.
Protein self-association may be detrimental in biological systems, but can be utilized in a controlled fashion for protein crystallization. It is hence of considerable interest to understand how factors like solution conditions prevent or promote aggregation. Here we present a computational model describing interactions between protein molecules in solution. The calculations are based on a molecular description capturing the detailed structure of the protein molecule using x-ray or nuclear magnetic resonance structural data. Both electrostatic and van der Waals interactions are included and the salt particles are explicitly treated allowing investigations of systems containing mono-, di-, and trivalent ions. For three different proteins-lysozyme, alpha-chymotrypsinogen, and calbindin D(9k)-we have investigated under which conditions (salt concentration, ion valency, pH, and/or solvent) the proteins are expected to aggregate via evaluation of the second virial coefficient. Good agreement is found with experimental data where available. Calbindin is investigated in more detail, and it is demonstrated how changes in solvent and/or counterion valency lead to attractive ion-ion correlation effects. For high valency counterions we have found abnormal trends in the second virial coefficient. With trivalent counterions, attraction of two negatively charged protein molecules can be favored because the repulsive term is decreased for entropic reasons due to the low number of particles present.
Binding Sites↗