Computational studies of enzymes

We are interested in the study of biochemical systems through the application of high-level quantum chemical methods. Chemical reactions when catalyzed by enzymes or when taking place in solution, are hard to handle through computation due to the large number of atoms involved. However, even in such systems, the reactions are usually confined to a small region which is usually termed as active site. Through the use of QM/MM approaches, this active site can be treated at a different level from the surrounding environment. Parameterized force fields are used in the description of the latter, while in the chemically relevant region, where quantum effects are significant, electronic structure approaches are used. Only through the combination of state-of-the-art quantum chemical methods and sampling techniques can one aim to accurately describe such complex processes.

Several of our most recent studies focus on the study of proton movement/diffusion in allosteric communication and in catalysis. These mechanisms appear to be recurrent through evolutionary pressure, potentially starting from simple aqueous environment reactivity. Further reading:
Nature 573, 609-613 (2019)
We have also collaborated with the Tittmann group in uncovering a new naturally occurring protein crosslink. The latter has been extensively characterised in our group. We are now in the process of studying the mechanism of its formation and the specific conditions required for this bond formation, particularly in competition with other pathways, such as disulfide bond formation or further oxidation of cysteine.
Nature, 593, 460 - 464 (2021)

Studies of reactivity and non-covalent interactions

Several of our projects are carried out in collaboration with other labs in our Faculty, including the Suhm, Alcarazo, Siewert and Meyer labs. Methodically, we are interested in exploring new coordinate spaces for the representation of reaction pathways, or which can speed up the process of discovery. Furthermore, we utilise wave function theory to analyse and interpret reactivity as well as non-covalent interactions in molecular systems, both in the gas and in condensed phase. A particular interest of the group has been the calculation of London dispersion forces. To the left one finds an example of such a study, the calculation of isomerisation pathways in substituted helicenes, which was recently highlighted in Chemistry, a European Journal.

Below you can find some recent examples:
Chemistry A European Journal, 27, 53, 13358 - 13366 (2021)
Inorg. Chem., 60, 1, 449 - 459 (2021)
Angewandte Chemie - International Edition 133, 1919 - 1924 (2021)

Local correlation methods

Local correlation methods are approaches to correlated wave function theory which offer low scaling of computational cost. Contrary to common codes, which scale exponentially with the system size, local methods can go down to scalar linear regimes. Several projects have been focused on local correlation methods, including the use of correlation regions, combination with continuum solvation models and visualisation of non-covalent interactions. We are at the moment working on the use of local orbital representations to derive diagnostics of correlated wave function calculations and also to improve on multicomponent methods.

Below you can find some examples of our work in this field:
Phys. Chem. Chem. Phys.,23, 12093 - 12104 (2021)
J. Chem. Theory Comput. 15, 922-937 (2019)
J. Chem. Theory Comput. 14, 5192-5202 (2018)