Molecular simulations of enzymes under non-natural conditions
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The development of novel sustainable biocatalytic processes requires systematic and comprehensive tools for engineering, integrated into a framework for the simultaneous optimization of enzyme, substrate, solvent, and reaction conditions. The experimentally determined biochemical properties of the biocatalyst are mediated by four interactions: between substrate and solvent, protein and solvent, protein and substrate, as well as protein–protein interactions. Molecular dynamics simulations were applied to study these interactions from first principles. The interaction of the substrate with the solvent was described by its activity coefficient, the interaction of the substrate with the protein and substrate access to the active site were characterized by a binding free energy along a reaction coordinate, and the protein–solvent interaction was modeled by a Langmuir model. The simulation of protein aggregation identified a delicate balance of kinetics and thermodynamics of competing contacts during the nucleation process.
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