Reaction Coordinate and Enhanced Sampling for Polymorph Nucleation

Nucleation as an essential pre-crystallization process is important in organic synthesis, drug industry and many other problems in science and engineering. However, given different conditions, different structures of specific molecules, also known as polymorphs, may form which eventually affect the performance of the compound synthesized. Many enhanced sampling based all-atom simulation methods have been developed to study the process of nucleation in systems with competing polymorphs, including entropic order parameters used with metadynamics [1,2]. Here we study such entropic and other order parameters to build an optimized low-dimensional reaction coordinate for biasing in metadynamics. To do so we use the method Spectral Gap Optimization of Order Parameters (SGOOP) [3]. With this we tackle different aspects of the nucleation process in classic problems [4] including the test-piece of urea polymorph nucleation.