Research Scientist, Computational Enzymology

Dayhoff Labs • Cambridge, MA

23h

About The Position

Simulate enzyme-catalysed reactions from the physics up, using reactive and free-energy methods to map reaction pathways in active sites, compute transition states and barriers, and determine the origins of catalysis. The role examines why reaction steps have particular barriers, which residues contribute to catalysis, and how mutations affect those barriers. The scientist will collaborate with simulation and machine-learning teams and work directly with bench scientists, with predictions tested in vitro and experimental feedback incorporated in rapid cycles.

Requirements

• Expertise in enzymatic reaction modelling using QM/MM and a variety of free-energy methods.
• A solid understanding of enzyme catalysis, including mechanisms, kinetics, cofactors, and how active-site chemistry and conformational dynamics determine rate and selectivity.
• Sound judgment in selecting methods, with a good understanding of methodological limitations and computational costs.

Nice To Haves

• Experience in protein design for enzymatic optimisation.
• Experience running design–test–refine cycles with a wet lab.
• Experience with reactive machine-learned potentials or coupling physics-based modelling with machine learning.

Responsibilities

• Characterise mechanisms, transition states, and activation barriers in enzyme active sites, and compare computed barriers with measured kinetics.
• Determine the residues, interactions, and dynamics that drive catalysis and influence rate and selectivity; use molecular dynamics to understand how active-site motion shapes reactions.
• Develop concrete, testable proposals for the wet lab and incorporate experimental results into models.
• Contribute to the development of physics-based and learned methods and help them strengthen one another.

What This Job Offers

• Job Type: Full-time
• Career Level: Senior
• Education Level: No Education Listed