Language models can generate molecules, materials, and protein binding
  sites directly in three dimensions as XYZ, CIF, and PDB files
Daniel Flam-Shepherd Alán Aspuru-Guzik
Language models are powerful tools for molecular design. Currently, the
dominant paradigm is to parse molecular graphs into linear string
representations that can easily be trained on. This approach has been very
successful, however, it is limited to chemical structures that can be
completely represented by a graph -- like organic molecules -- while materials
and biomolecular structures like protein binding sites require a more complete
representation that includes the relative positioning of their atoms in space.
In this work, we show how language models, without any architecture
modifications, trained using next-token prediction -- can generate novel and
valid structures in three dimensions from various substantially different
distributions of chemical structures. In particular, we demonstrate that
language models trained directly on sequences derived directly from chemical
file formats like XYZ files, Crystallographic Information files (CIFs), or
Protein Data Bank files (PDBs) can directly generate molecules, crystals, and
protein binding sites in three dimensions. Furthermore, despite being trained
on chemical file sequences -- language models still achieve performance
comparable to state-of-the-art models that use graph and graph-derived string
representations, as well as other domain-specific 3D generative models. In
doing so, we demonstrate that it is not necessary to use simplified molecular
representations to train chemical language models -- that they are powerful
generative models capable of directly exploring chemical space in three
dimensions for very different structures.