PT - JOURNAL ARTICLE
AU - Wang, Yaru
AU - Kruse, Holger
AU - Moriarty, Nigel W.
AU - Waller, Mark P.
AU - Afonine, Pavel V.
AU - Biczysko, Malgorzata
TI - Optimal clustering for quantum refinement of biomolecular structures: Q|R#4
AID - 10.1101/2022.11.24.517825
DP - 2022 Jan 01
TA - bioRxiv
PG - 2022.11.24.517825
4099 - http://biorxiv.org/content/early/2022/11/24/2022.11.24.517825.short
4100 - http://biorxiv.org/content/early/2022/11/24/2022.11.24.517825.full
AB - Quantum refinement (Q|R) of crystallographic or cryo-EM derived structures of biomolecules within the Q|R project aims at using ab initio computations instead of library-based chemical restraints. An atomic model refinement requires the calculation of the gradient of the objective function. While it is not a computational bottleneck in classic refinement it is a roadblock if the objective function requires ab initio calculations. A solution to this problem adopted in Q|R is to divide the molecular system into manageable parts and do computations for these parts rather than using the whole macromolecule. This work focuses on the validation and optimization of the automatic divide-and-conquer procedure developed within the Q|R project. Also, we propose an atomic gradient error score that can be easily examined with common molecular visualization programs. While the tool is designed to work within the Q|R setting the error score can be adapted to similar fragmentation methods. The gradient testing tool presented here allows a priori determination of the computationally efficient strategy given available resources for the potentially time-expensive refinement process. The procedure is illustrated using a peptide and small protein models considering different quantum mechanical (QM) methodologies from Hartree-Fock, including basis set and dispersion corrections, to the modern semi-empirical method from the GFN-xTB family. The results obtained provide some general recommendations for the reliable and effective quantum refinement of larger peptides and proteins.Competing Interest StatementThe authors have declared no competing interest.