(698k) Controlling Protein Crystallization through Wetting Near a Critical Point

We present results from large-scale molecular dynamics simulations on the crystallization of proteins, studying a family of minimal models for the nucleation of rubredoxin crystals. Our patchy shape model represents the protein by its realistic, three-dimensional shape and accounts both for specific interactions, which drive the assembly towards the target structure, and non-specific ones, which favor fluid-like states. Surprisingly, non-specific interactions enhance the nucleation rate by more than an order of magnitude. We highlight the important role of the fluid-solid interface and measure its interfacial tension. Our results agree qualitatively with the predicted wetting of nuclei near a fluid-fluid critical point, which in our system is metastable, as is often the case for proteins. Together, our results demonstrate how the concept of critically enhanced nucleation, introduced 20 years ago by ten Wolde and Frenkel for spherical particles, generalizes to a complex molecular system with anisotropy in shape and interaction. We therefore suggest a revised strategy for improving crystallization outcomes in experimental screens.