Premium
Refinement of protein structures using a combination of quantum‐mechanical calculations with neutron and X‐ray crystallographic data
Author(s) -
Caldararu Octav,
Manzoni Francesco,
Oksanen Esko,
Logan Derek T.,
Ryde Ulf
Publication year - 2019
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.374
H-Index - 138
ISSN - 2059-7983
DOI - 10.1107/s205979831900175x
Subject(s) - crystallography , neutron diffraction , molecule , chemistry , neutron , quantum , hydrogen bond , macromolecule , crystal structure , chemical physics , materials science , molecular physics , physics , quantum mechanics , biochemistry , organic chemistry
Neutron crystallography is a powerful method to determine the positions of H atoms in macromolecular structures. However, it is sometimes hard to judge what would constitute a chemically reasonable model, and the geometry of H atoms depends more on the surroundings (for example the formation of hydrogen bonds) than heavy atoms, so that the empirical geometry information for the H atoms used to supplement the experimental data is often less accurate. These problems may be reduced by using quantum‐mechanical calculations. A method has therefore been developed to combine quantum‐mechanical calculations with joint crystallographic refinement against X‐ray and neutron data. A first validation of this method is provided by re‐refining the structure of the galectin‐3 carbohydrate‐recognition domain in complex with lactose. The geometry is improved, in particular for water molecules, for which the method leads to better‐resolved hydrogen‐bonding interactions. The method has also been applied to the active copper site of lytic polysaccharide monooxygenase and shows that the protonation state of the amino‐terminal histidine residue can be determined.