Two-Step Mechanism of Macromolecular Nucleation and Crystallization: Field Theory and Simulations

Document Type

Article

Publication Date

1-6-2021

Abstract

We developed a phase-field method of simulations of crystallization of macromolecules from solutions, which provides a good combination of the efficiency, thermodynamic consistency, and predictive capability. The method allowed us to address some of the open questions of protein crystallization. The phase diagram of the solution contains low-density and high-density liquid and solid phases with the low-density liquid being the initial solution and the high-density solid being the final crystal. We observed three steps of the transformation process where the first step was homogeneous nucleation of the intermediate high-density liquid droplets, the second step was heterogeneous nucleation of the crystals on the droplet's surface, and the third step was dissolution of some of the crystallites and dense liquid droplets back into the liquid state of low density. We found the thermodynamic criterion of the two-step nucleation, which says that there is a gap of the overall initial solution concentrations below the liquidus where the one-step process is thermodynamically impossible. Beyond the gap, we observed a one-step transformation, which ended up with the formation of a phase morphologically similar to a gel. At large values of the liquid interaction coefficient and moderate values of the overall concentration, we observed the transformation scenario, which was reminiscent of the amorphous phase formation. The simulation results allowed us to suggest a resolution of the George-Wilson problem as the lack of dense liquid droplets for weak macromolecular attraction and ease of the amorphous phase formation for the strong attraction.

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