Understanding Ultrafast Isomerization Reactions – Insights from Hybrid QM/MM Simulations

Dr. Igor Schapiro

Title: Understanding Ultrafast Isomerization Reactions – Insights from Hybrid QM/MM Simulations.
When: 12:00 CET, Thursday, December 14th, 2023.
Place: Sala de Conferencias, Module 0, Faculty of Sciences, Autonomous University of Madrid (UAM).
Speaker: Dr. Igor Schapiro, Associate Professor at the Hebrew University of Jerusalem.

Photochemical reactions occur when light absorption alters the electronic structure of a molecule. Such changes permit to surpass activation barriers in a short period of time allowing reactions not accessible otherwise. One example of such a photochemical reaction is the primary event of vision in the vertebrate eye. The 11-cis-retinal protonated Schiff base (RPSB) bound to the visual protein rhodopsin (Rh) photoisomerizes to the all-trans isomer1. With a ~100% selectivity, ~65% quantum yield, and ~200 fs product appearance time, this isomerization is considered the archetype of a photochemical reaction optimized by nature to achieve a specific molecular response.
We have used a combination of a quantum chemical and a classical force field method (QM/MM) to resolve the isomerization mechanism in different protein environments. In particular, we have studied the photoisomerization of the recently discovered bestrophin-rhodopsin2, where the protein environment was found to control the selectivity of the isomerizing bond.
In addition, we have studied the photoreaction of an azobenzene derivative of the anticancer drug combretastatin A4 bound to tubulin3. The results of our hybrid QM/MM simulations were compared to experimental counterparts from time-resolved crystallography on the femtosecond timescale.

References:
1. Gruhl T, Weinert T, Rodrigues MJ, Milne CJ, Ortolani G, et al. Nature 2023, 615, 939-44.
2. Rozenberg A, Kaczmarczyk I, Matzov D, Vierock J, Nagata T, et al. Nature Struct. Mol. Biol. 2022, 29, 592-603.
3. Wranik M, Weinert T, Slavov C, Masini T, Furrer A, et al. Nature Commun. 2023, 14, 903.

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