Quantum chemical studies of biochemical reaction mechanisms
Title: |
Quantum chemical studies of biochemical reaction mechanisms |
DNr: |
NAISS 2024/22-1540 |
Project Type: |
NAISS Small Compute |
Principal Investigator: |
Per Siegbahn <ps@organ.su.se> |
Affiliation: |
Stockholms universitet |
Duration: |
2024-12-01 – 2025-12-01 |
Classification: |
10407 |
Keywords: |
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Abstract
This application concerns computer resources for studying mechanisms
of redox active enzymes. During the past period, the studies have been
performed on Tetralith at NSC. Using hybrid density functional theory and active
site models of 100-400 atoms, potential energy surfaces for different
mechanisms are calculated. The computed results are compared to
experimental reaction rates and other observations. There have been
four major projects the past decade. The first one is ammonia formation in nitrogenase. A new mechanism has been suggested which includes an activation prior to catalysis. Since the mechanism is debated, new informtion from model calculations is required. It is expected that this project is going to be the main one the coming years. The second one is water oxidation in photosystem II, for which results superior to experiments for both structures and mechanisms have been obtained. New alternative mechanisms have been suggested in the literature, and comparisons to our mechanism needs to be studied requiring new calculations. The third one is oxygen reduction and proton pumping in cytochrome c oxidase in the respiratory chain. During recent years a mechanism has been obtained, which so far is the only one that stands all experimental observations. During the past year, new very conclusive experimental
studies have been published in Science and JACS, by leading experimental groups in this area. The mechanism proposed by our group is confirmed in utmost detail. The fourth one concerns studies of laboratory mimics of the above enzymes. Other examples of enzyme redox mechanisms have been described in a recent comprehensive review in Chemical Reviews. It is of large importance that these projects, which are at the top of similar projects in the world, continues to be supported by computer funding.