Macromolecular refinement uses simple geometry constructs to provide the best atomic coordinates of a large molecule that can contain protein, nucleic acids, carbohydrates, metal ions, water and ligands. The geometry constructs are weighed against experiments such as x-ray crystallography, neutron crystallography, cryo-electron microscopy and XFEL. The simple constructs known as restraints can be derived from experimental databases or increasingly quantum mechanics. MOPAC has been deployed to generate restraints for isolated ligands for at least two decades in Phenix (Liebschner et al., 2019) but recently, the tools to calculate in situ geometries for ligands in protein binding pockets (Liebschner et al., 2023) has improved the restraints used in refinement. Additional applications of this technique include metal coordination, nonstandard amino acids, unusual linakges and relaxation energies.
Liebschner, D., Afonine, P. V., Baker, M. L., Bunkóczi, G., Chen, V. B., Croll, T. I., Hintze, B., Hung, L.-W., Jain, S., McCoy, A. J., Moriarty, N. W., Oeffner, R. D., Poon, B. K., Prisant, M. G., Read, R. J., Richardson, J. S., Richardson, D. C., Sammito, M. D., Sobolev, O. V., Stockwell, D. H., Terwilliger, T. C., Urzhumtsev, A. G., Videau, L. L., Williams, C. J. & Adams, P. D. (2019). Acta Cryst D 75, 861–877.
Liebschner, D., Moriarty, N. W., Poon, B. K. & Adams, P. D. (2023). Acta Cryst D 79, 100–110.