Extension of the Hirshfeld atom refinement technique to macromolecules
Hirshfeld atom refinement (HAR) is an emerging refinement technique of crystallography strongly based on quantum chemistry concepts and calculations. Recent studies have shown that, exploiting only X-ray diffraction data at resolutions as low as 0.8 Å, the method allows the determination of hydrogen atoms positions as accurately and precisely as from neutron diffraction measurements.
In principle, given the excellent results obtained for small organic molecules, HAR could be also used to refine crystal structures of macromolecules (e.g., proteins). Nevertheless, since the strategy requires a tailor-made quantum mechanical calculation for each step of the refinement, its extension to large system is prevented by the large computational cost. To overcome this drawback, in collaboration with Simon Grabowsky (University of Bern), we have coupled HAR with our ELMO libraries, which enable to quickly compute approximate wave functions of macromolecules. The developed HAR-ELMO method has been applied to polypeptides and small proteins and allowed significant reductions in terms CPU time compared to the traditional Hirshfeld atom refinements, without affecting the accuracy the results. To further improve the technique, we are currently coupling HAR with our fully quantum mechanical embedding approach QM/ELMO, which will hopefully allow better crystal structure refinements for crucial regions of proteins (e.g., active sites or metal centers in metalloproteins). |
Representative publications
- L. A. Malaspina, E. K. Wieduwilt, J. Bergmann, F. Kleemiss, B. Meyer, M. F. Ruiz-López, R. Pal, E. Hupf, J. Beckmann, R. O. Piltz, A. J. Edwards, S. Grabowsky, A. Genoni*
The Journal of Physical Chemistry Letters 10, 6973-6982 (2019)
- E. K. Wieduwilt, G. Macetti, A. Genoni*
of Hydrogen Atom Positions
The Journal of Physical Chemistry Letters 12, 463-471 (2021)