Home Institute: Zymvol Biomodeling S.L., Spain
Main supervisors: Ferran Sancho and
Maria Fátima Lucas
Co-Supervisors: Lígia Martins (UNL) and
Nikola Loncar (GECCO)
Required academic background: Computer Engineering or scientist with strong coding skills.

In this project, cutting-edge computational methods will be employed to discover and engineer enzymes for polymer functionalization, with a particular focus on transaminases. Two in-house pipelines will be adapted to accept polymers as a substrate: BioMatchMaker (BMM) for enzyme discovery and Zymevolver (ZYV) for enzyme engineering. ZYV is an efficient pipeline that combines bioinformatics, including statistical analysis of databases, with robust physics-based simulations at various theoretical levels to model enzymatic complexes accurately. BMM, on the other hand, enables the exploration of the enzyme sequence space through modeling and docking techniques. It progressively filters sequences until 10-20 sequences are selected for laboratory testing. The main goal of this project is to prepare pipelines for high-throughput screening of enzymes, both for enzyme discovery and engineering. Significantly, the potential of state-of-the-art deep-learning algorithms will be explored and optimized for discovering and engineering enzymes for polymer functionalization or degradation purposes.  

Objectives:

  • Acquiring in-depth knowledge of the protein-ligand system through literature review and computational modeling.

  • Adaptation of in-house pipelines for optimizing polymer-protein interactions.

  • In silico engineering of a transaminase by predicting hot spots and mutations.

  • Deep-learning-based discovery and engineering, using data generated in the lab (and by other partners) for model optimization.

  • Discovery of an ADH/TAM pair of enzymes to catalyze a new molecule’s hydroxyl to amine transformation.

Expected results:

  • Better computational understanding of transaminases.

  • Quality data for ML purposes.

  • New transaminase variant with improved activity towards hexanone.

  • New ADH/TAM system for catalysis of the cascade reaction from alcohol to amine.