| 1. |
- Pasquier, Coralie, et al.
(författare)
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Anisotropic protein-protein interactions in dilute and concentrated solutions
- 2023
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797. ; 629, s. 794-804
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Tidskriftsartikel (refereegranskat)abstract
- Interactions between biomolecules are ubiquitous in nature and crucial to many applications including vaccine development; environmentally friendly textile detergents; and food formulation. Using small angle X-ray scattering and structure-based molecular simulations, we explore protein–protein interactions in dilute to semi-concentrated protein solutions. We address the pertinent question, whether interaction models developed at infinite dilution can be extrapolated to concentrated regimes? Our analysis is based on measured and simulated osmotic second virial coefficients and solution structure factors at varying protein concentration and for different variants of the protein Thermomyces Lanuginosus Lipase (TLL). We show that in order to span the dilute and semi-concentrated regime, any model must carefully capture the balance between spatial and orientational correlations as the protein concentration is elevated. This requires consideration of the protein surface morphology, including possible patch interactions. Experimental data for TLL is most accurately described when assuming a patchy interaction, leading to dimer formation. Our analysis supports that the dimeric proteins predominantly exist in their open conformation where the active site is exposed, thereby maximising hydrophobic attractions that promote inter-protein alignment.
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| 2. |
- Pasquier, Coralie, et al.
(författare)
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Anomalous Protein-Protein Interactions in Multivalent Salt Solution
- 2017
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 121:14, s. 3000-3006
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Tidskriftsartikel (refereegranskat)abstract
- The stability of aqueous protein solutions is strongly affected by multivalent ions, which induce ion-ion correlations beyond the scope of classical mean-field theory. Using all-atom molecular dynamics (MD) and coarse grained Monte Carlo (MC) simulations, we investigate the interaction between a pair of protein molecules in 3:1 electrolyte solution. In agreement with available experimental findings of "reentrant protein condensation", we observe an anomalous trend in the protein-protein potential of mean force with increasing electrolyte concentration in the order: (i) double-layer repulsion, (ii) ion-ion correlation attraction, (iii) overcharge repulsion, and in excess of 1:1 salt, (iv) non Coulombic attraction. To efficiently sample configurational space we explore hybrid continuum solvent models, applicable to many-protein systems, where weakly coupled ions are treated implicitly, while strongly coupled ones are treated explicitly. Good agreement is found with the primitive model of electrolytes, as well as with atomic models of protein and solvent.
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| 3. |
- Pasquier, Coralie, et al.
(författare)
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Osmotic pressures of lysozyme solutions from gas-like to crystal states
- 2016
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Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 18:41, s. 28458-28465
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Tidskriftsartikel (refereegranskat)abstract
- We obtained osmotic pressure data of lysozyme solutions, describing their physical states over a wide concentration range, using osmotic stress for pressures between 0.05 bar and about 40 bar and volume fractions between 0.01 and 0.61. The osmotic pressure vs. volume fraction data consist of a dilute, gas-phase regime, a transition regime with a high-compressibility plateau, and a concentrated regime where the system is nearly incompressible. The first two regimes are shifted towards a higher protein volume fraction upon decreasing the strength or the range of electrostatic interactions. We describe this shift and the overall shape of the experimental data in these two regimes through a model accounting for a steric repulsion, a short-range van der Waals attraction and a screened electrostatic repulsion. The transition is caused by crystallization, as shown by small-angle X-ray scattering. We verified that our data points correspond to thermodynamic equilibria, and thus that they consist of the reference experimental counterpart of a thermodynamic equation of state.
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| 4. |
- Polimeni, Marco, et al.
(författare)
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Virtual cell model for osmotic pressure calculation of charged biomolecules
- 2021
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 155:19
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Tidskriftsartikel (refereegranskat)abstract
- The osmotic pressure of dilute electrolyte solutions containing charged macro-ions as well as counterions can be computed directly from the particle distribution via the well-known cell model. Originally derived within the Poisson-Boltzmann mean-field approximation, the cell model considers a single macro-ion centered into a cell, together with counterions needed to neutralize the total cell charge, while it neglects the phenomena due to macro-ion correlations. While extensively applied in coarse-grained Monte Carlo (MC) simulations of continuum solvent systems, the cell model, in its original formulation, neglects the macro-ion shape anisotropy and details of the surface charge distribution. In this paper, by comparing one-body and two-body coarse-grained MC simulations, we first establish an upper limit for the assumption of neglecting correlations between macro-ions, and second, we validate the approximation of using a non-spherical macro-ion. Next, we extend the cell model to all-atom molecular dynamics simulations and show that protein concentration-dependent osmotic pressures can be obtained by confining counterions in a virtual, spherical subspace defining the protein number density. Finally, we show the possibility of using specific interaction parameters for the protein-ion and ion-ion interactions, enabling studies of protein concentration-dependent ion-specific effects using merely a single protein molecule.
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