Validated ligand geometries for macromolecular refinement restraints and molecular-mechanics force fields.

Journal Article · Sun Mar 01 00:00:00 EST 2026 · Acta Crystallographica Section D - Structural Biology

DOI:https://doi.org/10.1107/s2059798326000975· OSTI ID:3030156

Moriarty, Nigel W; Case, David A; Liebschner, Dorothee; Adams, Paul D

In macromolecular structure refinement, the low observation-to-parameter ratio and the lack of high-resolution data are countered by using a priori information in the form of restraints. Having accurate geometries of the chemical entities in the sample is paramount for generating accurate chemical restraints and, therefore, accurate macromolecular structures. In particular, it is desirable to have accurate restraints for known and novel ligand entities. Quantum mechanics (QM) can minimize the energy of a ligand by adjusting its geometry, and these geometries can be used to generate restraints for macromolecular refinement. This article describes a library of approximately 37 000 small molecules extracted from the Chemical Component Dictionary in the Protein Data Bank and minimized by density-functional QM. The library includes restraint files for use in crystallography or cryo-EM refinement, along with files suitable for molecular-dynamics simulation. Because the geometries are validated using the Cambridge Structural Database, the restraints library provides users with both functional restraints and minimized geometries. This work also provides procedures for generating new and accurate restraints.

• Research Organization: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
• Sponsoring Organization: US Department of Energy; USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23), Biological Systems Science Division (SC-23.2 )
• Grant/Contract Number: AC02-05CH11231
• OSTI ID: 3030156
• Journal Information: Acta Crystallographica Section D - Structural Biology, Journal Name: Acta Crystallographica Section D - Structural Biology Journal Issue: 3 Vol. 82
• Country of Publication: United States
• Language: English