Clusters of lysozyme in aqueous solutions

Abstract

Equilibrium clusters of protein lysozyme are at the center of an ongoing scientific debate. Previous attempts to provide a microscopic description of the clusters that is consistent with all experimental evidence have not been fully successful. The primary reason is the use of model potentials that have a predefined shape. In this paper we derive a model-free interprotein potential directly from experimental structure factor. The derived potential is globally repulsive but has a local minimum at short distances. The minimum is essential for the correct behavior of the structure factor with protein concentration, in particular the shifting pattern of the signature maximum at short wave vectors. Equilibrium clusters are observed throughout the entire range of concentrations, but their nature differs in the low and high concentration limits. At low concentrations, the clusters are extended in shape. As the concentration is increased, small clusters collapse while large clusters are assembled from the small ones. Hydrodynamic interactions drive a kinetic slowdown at high concentrations, where a transition into a fluid of permanent clusters of specific size is observed. In good agreement with the available experimental data, our simulations shed light on the microscopic nature of protein clusters.