In Silico Design of Enzymes to Degrade Short-chain Per- and Polyfluoroalkyl Substances (PFAS)

Presenter: Salomé Guilbert PhD (salome.guilbert@epfl.ch)

Authors:
Salomé Guilbert PhD¹; Prof. Philippe Schwaller²; Prof. Ursula Roethlisberger²

¹ Ecole Polytechnique Fédérale Lausanne; ² EPFL

Increasing concern over the persistence and toxicity of per- and polyfluoroalkyl substances (PFAS) has pushed for the need to design technologies for their remediation. To date, the only commercially degradation method involves costly and unsustainable thermal deconstruction. Bioremediation stands as an attractive, cost-effective and sustainable solution for degrading such pollutants, although few bacteria and no enzymes are known to achieve the full degradation of PFAS.

The in silico rational design of novel enzymes for PFAS degradation first involved the selection of a suitable biological target that had the potential to be optimised for better substrate binding, catalytic activity and thermal stability. A theozyme was created with the catalytic residues of fluoroacetate dehalogenase, a well-studied enzyme capable of breaking the strong carbon-fluorine bond (460 kJ/mol) in fluoroacetate. First, RFDiffusionAA helped generate a library of suitable scaffolds around the theozyme. After sequence design with ProteinMPNN, AlphaFold was used to filter the sequences that folded in the desired structures.

To assess the catalytic reaction of these enzyme designs, QM/MM simulations will be performed. Further, selected biomimetic systems will be optimised with genetic algorithms, classical molecular simulations and machine learning tools such as AI.Zymes. This process will be applied to short-chain PFAS molecules, often overlooked as degradation products of longer-chain PFAS.

 

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