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Novel Multidimensional Enzyme Reaction Dynamics method reported in ACS Catalysis

23 Mar 2017 - 06:15

The suppression of competing reactions that lead to side products is one of the key mechanistic actions defining enzyme catalysis. The transfer of sialic acid (SA) in a water solution is susceptible to two competing side reactions, but a single product is the outcome in the glycosylation and deglycosylation steps of the trans-sialidase (TS) in the Trypanosoma cruzi (T. cruzi) parasite, generally known as TcTS. We use multidimensional QM/MM free energy computations to reveal a competition between a minor elimination reaction and the dominant displacement reaction present in both steps. The simultaneous monitoring of the progression of the competing reactions reveals lower barriers in the free energy profiles, a greater sampling of favorable reactant stereoelectronic alignments, and a greater number of possible transition paths leading to successful crossing reaction trajectories for the dominant displacement reactions in comparison with those of the elimination reactions.

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