Research

Main topics of research in the group

Enzymatic Systems

A central theme of our research is the application of high-level quantum chemical methods to the study of biochemical processes. We use QM/MM (quantum mechanics / molecular mechanics) approaches to treat enzyme active sites at the quantum level while describing the surrounding protein environment with classical force fields. This allows us to obtain quantitatively accurate results for enzyme reaction mechanisms with full account of the protein environment.

Current interests include the role of proton transfer steps in catalysis, allosteric communication in multimeric enzymes, and the chemistry of naturally occurring covalent crosslinks in proteins. Recent highlights include the characterization of low-barrier hydrogen bonds in enzyme cooperativity (Nature 573, 2019), the discovery of widespread lysine–cysteine NOS-bridge redox switches (Nat. Chem. Biol. 18, 2022), redox switch mechanisms in the SARS-CoV-2 main protease (Nat. Commun. 15, 2024), and the mechanistic study of cysteine–lysine covalent linkage formation in enzymes. We have also contributed to the analysis of protonation states in ThDP-dependent enzymes and to disproving ground-state destabilization as a catalytic driving force in OMP decarboxylase.

Key publications:
  • Dai et al., Nature 573, 609–613 (2019) — DOI
  • Wensien et al., Nature 593, 460–464 (2021) — DOI
  • Rabe von Pappenheim et al., Nat. Chem. Biol. 18, 368–375 (2022) — DOI
  • Rindfleisch et al., Nat. Catal. 5, 332–341 (2022) — DOI
  • Ye, Bazzi, Fritz, Tittmann, Mata & Uranga, Angew. Chem. Int. Ed. 62, e202304163 (2023) — DOI
  • Uranga & Mata, J. Chem. Inf. Model. 63, 3118–3127 (2023) — DOI
  • Uranga, Rabe von Pappenheim, Tittmann & Mata, J. Phys. Chem. B 127, 7744–7754 (2023) — DOI
  • Funk et al., Nat. Commun. 15, 136 (2024) — DOI
  • Schrader et al., Science 353, 594–598 (2016) — DOI

Reactivity and Non-Covalent Interactions

We carry out collaborative projects examining reaction pathways and non-covalent interactions using wave function theory methods in both gas phase and condensed phases. A particular interest lies in London dispersion forces, which play a critical role in the stabilization of chemical systems ranging from small molecular clusters to large supramolecular assemblies. Recent work has examined how dispersion can be purposefully controlled to tune reactivity and selectivity — a concept we term “aromatic tipping power”.

This work includes accurate computational benchmarking of non-covalent interaction energies, studies of chirality recognition driven by dispersion forces, and mechanistic investigations of transition metal catalyzed reactions. We collaborate closely with experimental groups, particularly in the context of the BENCh RTG2455 research training group and the qmbench initiative. The group has organized and participated in community blind benchmarking challenges — including HyDRA (vibrational spectroscopy of hydrates) and Fe-MAN (organometallic reactivity) — to rigorously test computational methods against experimental reference data.

Key publications:
  • Mata & Suhm, Angew. Chem. Int. Ed. 56, 11011–11018 (2017) — DOI
  • Aniban et al., Phys. Chem. Chem. Phys. 23, 12093–12104 (2021) — DOI
  • Fischer, Bödecker et al., Phys. Chem. Chem. Phys. 25, 22089–22102 (2023) — DOI
  • Mata, Zehnacker-Rentien & Suhm, Phys. Chem. Chem. Phys. 25, 26415–26416 (2023) — DOI
  • Mata et al., Acc. Chem. Res. 57, 1077–1086 (2024) — DOI
  • Rahrt, Hein-Janke et al., J. Phys. Chem. A 128, 4663–4673 (2024) — DOI

Multicomponent Methods and Nuclear Quantum Effects

We develop and apply multicomponent quantum chemistry methods based on the nuclear–electronic orbital (NEO) framework, in which selected nuclei — typically protons — are treated quantum mechanically alongside the electrons. This goes beyond the Born–Oppenheimer approximation and intrinsically captures nuclear quantum effects such as zero-point energy, nuclear delocalization, and anharmonicity, without requiring an explicit potential energy surface.

Key methodological contributions from the group include: local density fitting for multicomponent methods (making NEO calculations computationally accessible); adaptive geometry optimization of quantum nuclei positions; local electronic correlation (PNO-based) in multicomponent MP2; density-fitted multicomponent DFT for anharmonic zero-point energies; and multicomponent double-hybrid density functional theory. Applications focus on predicting anharmonic vibrational frequencies (especially O–H stretching shifts in hydrogen-bonded complexes), conformational energetics where zero-point energy differences are decisive, and proton dynamics. The methods are implemented in the Molpro quantum chemistry package. This program builds on the group’s longstanding expertise in local correlation methods and extends it into a distinct new direction for treating nuclear quantum effects directly at the wave function level.

Key publications:
  • Hasecke & Mata, J. Chem. Theory Comput. 19, 8223–8233 (2023) — DOI
  • Hasecke & Mata, J. Phys. Chem. A 128, 3205–3211 (2024) — DOI
  • Hasecke & Mata, J. Chem. Theory Comput. 20, 9928–9938 (2024) — DOI
  • Hasecke, Breitenbach, Gimferrer, Oswald & Mata, J. Phys. Chem. A 129, 3560–3566 (2025) — DOI
  • Hasecke & Mata, J. Chem. Theory Comput. 21, 11509–11520 (2025) — DOI
  • Gimferrer, Hasecke, Bödecker & Mata, Chem. Sci. 16, 11002–11011 (2025) — DOI
  • Mata, Werner & Schütz, J. Chem. Phys. 128, 144106 (2008) — DOI
  • Feldt & Mata, J. Chem. Theory Comput. 14, 5192–5202 (2018) — DOI

Software and Benchmark Initiatives

Alongside method development, the group contributes software tools and community benchmarking initiatives that bridge computation and experiment. The qmbench platform coordinates blind prediction challenges — including HyDRA (vibrational spectroscopy of hydrates) and Fe-MAN (organometallic reactivity) — in which computational methods are tested against experimental reference data before results are revealed. Multicomponent NEO methods are implemented in Molpro. The chemcoord library provides automated handling of complex molecular geometries in Z-matrix coordinates (Weser, Hein-Janke & Mata, J. Comput. Chem. 44, 710–726, 2023 — DOI). The group also contributes to NFDI4Chem, the national research data management infrastructure for chemistry. Additional tools are available via the group GitHub.