In this project we are investigating the effect of anisotropy or patchiness on protein-protein interactions, using detailed Metropolis Monte Carlo computer simulations in combination with static light scattering and SAXS. The Monte Carlo simulations have been combined with static light scattering (SLS) measurements of the second viral coefficient to provide insights into the mechanism of patchy, attractive protein interactions. We use lactoferrin as model protein, since it was predicted to display anisotropic attractive interactions and the calculated values of protein-protein interactions from the simulations leads to a good quantitative agreement with the experimental data, using no adjustable parameters. The molecular origin of the attraction could be explained as a combination of a highly directional electrostatic contribution, a local charged patch, and van der Waals attraction. This gives rise to two competing electrostatic effects acting over different length scales, which is seen as an anomalous dependence in the second virial coefficient as a function of electrolyte concentration (Li et al., JPhys. Chem. B, 2015). Similar salt dependence has been observed in various proteins which points to a more general mechanism.  Currently the effect of the attraction anisotropy on the scattering pattern is being explored. Recombinant variant of lactoferrin are currently being expressed in collaboration with LP3, the protein production platform at Lund University.

People: Weimin Li, Björn Persson (Division of Theoretical Chemistry), Mikael Lund (Division of Theoretical Chemistry), Johan Bergenholtz and Malin Zackrisson Oskolkova

Contact person: Malin Zackrisson Oskolkova