title: Pound-wise but penny-foolish: How well do micromolecules fare in macromolecular refinement?
abstract: For the refinement of protein and nucleic acid structures, high-quality geometric restraint libraries are available. Unfortunately, for other compounds, such as physiological ligands, lead compounds, substrate analogs, etc., the situation is not as favorable. As a result, the structures of small molecules found in complexes with biomacromolecules are often less reliable than those of the surrounding amino or nucleic acids. Here, we briefly review the use of geometric restraints in structure refinement (be it against X-ray crystallographic or NMR-derived data) and simulation. In addition, we discuss methods to generate both restraint libraries and (idealized) coordinates for small molecules and provide some practical advice.
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Biomedical Centre, Box 596, SE-751 24 Uppsala, Sweden. gerard@xray.bmc.uu.se
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Kleywegt
authors.forename: Kim
authors.initials: K
authors.lastname: Henrick
authors.forename: Eleanor J
authors.initials: EJ
authors.lastname: Dodson
authors.forename: Daan M F
authors.initials: DM
authors.lastname: van Aalten
mesh_terms: D019295:Computational Biology; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D046911:Macromolecular Substances