Using the Quantum Interface in Phenix to improve macromolecular model and ligand structures
Abstract
Quantum Mechanical methods provide geometries and energies of molecules using just the atomic and electronic positions. Being independent of the experimental data, they provide complementary information. Furthermore, allowing the experimental and QM methods to share information leads to better results.
The Quantum Interface (QI) in Phenix (Liebschner et al., 2019) provides close integration with MOPAC (Moussa & Stewart, 2024) allowing the calculation of in situ restraints for drug candidates. Known as QM Restraints (QMR) (Liebschner et al., 2023), this method will provide protein binding pocket specific restraints during a refinement or in a stand-alone program.
Another QI procedure is a novel approach for predicting histidine protonation states using QM methods. Historically, determining histidine protonation has been challenging due to limited resolution in X-ray crystallography and the inherent difficulty in detecting hydrogen atoms. Previous methods relied on empirical or geometric models, which provided some insights but had limitations.
The proposed method, Quantum Mechanical Flipping (QMF) (Moriarty et al., In review), employs quantum mechanical calculations to predict protonation states based on the molecular environment. This approach considers all possible configurations of histidine protonation and assesses their feasibility by minimising geometry and energy calculations. QMF accounts for factors such as hydrogen bonding and molecular interactions providing a more…
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