Led by Prof. Adrian Mulholland (University of Bristol)
The project “Advanced Computation for Hybrid Biocatalyst Design,” led by Prof Adrian Mulholland (University of Bristol) with PDRA Marko Hanzevački, will establish a powerful digital framework for the next generation of hybrid biocatalysts.
Bringing together advanced quantum chemical modelling, multiscale simulation and deep-learning protein design tools, the project aims to move beyond the natural catalytic repertoire by installing new-to-nature chemical functionalities into both natural and de novo protein scaffolds. By integrating state-of-the-art protein structure prediction and design platforms with QM/MM methods, molecular dynamics and electric-field optimisation strategies, the team will create robust workflows for modelling transition states, excited states and reaction intermediates in artificial metalloenzymes and photoenzymes. A central deliverable will be a curated database of catalytic templates and transition states to drive rational biocatalyst design, supported by AI and machine learning approaches that combine structural, mechanistic and bioinformatic data across the Hub.
This programme exemplifies the Digital Catalysis theme by embedding computation, data science and collaborative virtual design tools at the heart of catalyst discovery. The project will develop predictive workflows that guide directed evolution, enable the incorporation of noncanonical amino acids and unnatural metal centres, and optimise electric fields within catalytic sites—an emerging frontier in enzyme design. Applications target Net Zero-relevant challenges, including nitrogen fixation, sustainable fine chemical synthesis, artificial photosynthesis and carbon capture, as well as chemo/biocatalytic hybrid processes that reduce energy, solvent and precious metal requirements. Working closely with experimental partners, predictions will directly inform catalyst construction and validation, creating a seamless digital–experimental loop and delivering a broadly accessible platform for hybrid biocatalyst engineering across the Catalysis Hub and beyond.
