fragHAR: towards ab initio quantum-crystallographic X-ray structure refinement for polypeptides and proteins

Justin Bergmann; Max Davidson; Esko Oksanen; Ulf Ryde; Dylan Jayatilaka

doi:10.1107/S2052252519015975

fragHAR: towards ab initio quantum-crystallographic X-ray structure refinement for polypeptides and proteins

IUCrJ. 2020 Jan 17;7(Pt 2):158-165. doi: 10.1107/S2052252519015975. eCollection 2020 Mar 1.

Authors

Justin Bergmann¹, Max Davidson², Esko Oksanen³, Ulf Ryde¹, Dylan Jayatilaka²

Affiliations

¹ Department of Theoretical Chemistry, Chemical Center, Lund University, PO Box 124, SE-221 00 Lund, Sweden.
² School of Molecular Sciences M310, University of Western Australia, 35 Stirling Highway, Crawley 6009, Australia.
³ Instruments Division, European Spallation Source ESS ERIC, PO Box 176, SE-221 00 Lund, Sweden.

Abstract

The first ab initio aspherical structure refinement against experimental X-ray structure factors for polypeptides and proteins using a fragmentation approach to break up the protein into residues and solvent, thereby speeding up quantum-crystallographic Hirshfeld atom refinement (HAR) calculations, is described. It it found that the geometric and atomic displacement parameters from the new fragHAR method are essentially unchanged from a HAR on the complete unfragmented system when tested on dipeptides, tripeptides and hexapeptides. The largest changes are for the parameters describing H atoms involved in hydrogen-bond interactions, but it is shown that these discrepancies can be removed by including the interacting fragments as a single larger fragment in the fragmentation scheme. Significant speed-ups are observed for the larger systems. Using this approach, it is possible to perform a highly parallelized HAR in reasonable times for large systems. The method has been implemented in the TONTO software.

Keywords: H atoms; Hirshfeld atom refinement; peptides; quantum crystallography.

Grants and funding

This work was funded by Svenska Forskningsrådet Formas grant 2018-05003 to Ulf Ryde. Department of Industry, Innovation, Science, Research and Tertiary Education, Australian Government grant .