  Understanding the driving forces behind the nucleation of different
polymorphs is of great importance for material sciences and the pharmaceutical
industry. This includes understanding the reaction coordinate that governs the
nucleation process as well as correctly calculating the relative free energies
of different polymorphs. Here we demonstrate, for the prototypical case of urea
nucleation from melt, how one can learn such a 1-dimensional reaction
coordinate as a function of pre-specified order parameters, and use it to
perform efficient biased all-atom molecular dynamics simulations. The reaction
coordinate is learnt as a function of generic thermodynamic and structural
order parameters using the "Spectral Gap Optimization of Order Parameters
(SGOOP)" approach [P. Tiwary and B. J. Berne, Proc. Natl. Acad. Sci. (2016)],
and is biased using well-tempered metadynamics simulations. The reaction
coordinate gives insight into the role played by different structural and
thermodynamics order parameters, and the biased simulations obtain accurate
relative free energies for different polymorphs. This includes accurate
prediction of the approximate pressure at which urea undergoes a phase
transition and one of the metastable polymorphs becomes the most stable
conformation. We believe the ideas demonstrated in thus work will facilitate
efficient sampling of nucleation in complex, generic systems.
