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

2026/02/11 by Nigel W. Moriarty, David A. Case, Dorothée Liebschner +1 · 1 voice
Biochemistry, Genetics and Molecular Biology · Materials Science · #Advanced Electron Microscopy Techniques and Applications #Enzyme Structure and Function #Protein Structure and Dynamics

paper · doi:10.1107/s2059798326000975

openalex publication_date 2026/02/11 · openalex created_date 2026/02/19 · openalex updated_date 2026/07/31

Abstract

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.

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