Metadynamics study of protein crystal nucleation and growth*

Using a coarse-grained, solvent-free rigid body model of a model protein, we
study the role of shape and nonspecific interaction in the nucleation of the
protein crystal. We parameterize our patchy shape model using information from
experimentally observed molecular and crystal structures, which ensures
self-assembly into the correct target crystal structure. We use well-tempered
Metadynamics to quantify the free energy of the liquid and crystal states and
determine the height of the nucleation barrier. Remarkably, even when
interactions are entirely nonspecific, the system minimizes its free energy
through shape-induced fit and is still capable of assembling the target
structure in biased simulations.