Multiscale modeling of charge transfer reactions in biological systems

In many biological systems charge transfer reactions are crucial steps in carrying out different functions, such as energy conversion in photosynthesis and respiration, light-activated proton pumping in rhodopins and polypeptide cleavage in proteases. I will present the investigation of a proton transfer (PT) and a light-induced electron transfer (ET) reaction by means of a multiscale computational approach.
The PT reaction is the first step of the catalytic reaction in SARS-CoV-2 main protease. This protein plays a key role in viral replication and transcription, cleaving the virus non-structural polyprotein.
Inhibition of its activity would therefore block the viral replication cycle. The cleavage activity is activated by a PT at the active site, and the same reaction is also required for the covalent binding of inhibitors. We investigated the PT thermodynamics in the apo enzyme and in complex with two promising inhibitors.
The ET reaction is a light-induced reaction in a flavoenzyme, lactate monooxygenase, that is a good platform for non-natural photoenzymatic catalysis. We investigate the photo-initiated ET at the flavin mononucleotide binding site, also in comparison with experimental data from ultrafast spectroscopy, providing mechanistic insights into the photochemistry of the enzyme.

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