Research

Multiscale mechanisms and molecular design.

We integrate QM/MM reaction-path sampling, atomistic molecular dynamics, enhanced sampling and kinetic models to connect microscopic mechanisms with thermodynamic and experimental observables.

01

Catalysis & reaction mechanisms

Resolve chemical reactivity in heterogeneous biomolecular environments.

Enzymes accelerate reactions through a precisely organised network of electrostatics, proton transfers, metal coordination and conformational motion. We use quantum mechanics/molecular mechanics calculations to resolve these contributions and test competing mechanistic hypotheses.

Phosphate chemistry

Hydrolysis and transfer reactions in nucleotide-processing and signalling enzymes.

Metalloenzymes

Metal identity, coordination geometry and their influence on selectivity and reaction barriers.

Protein redesign

Mechanism-based sequence changes that recover or reshape catalytic activity.

QM/MM workflows

Reaction paths, free-energy profiles and high-level electronic-structure refinement.

Reaction schemes, enzyme statistics and active-site structures illustrating the Mg-pinch motif
Mg-pinch coordination in NTP phosphatase and pyrophosphatase chemistry. Dudás et al., JACS 2026, CC BY 4.0.
02

Free energies, kinetics & pathways

Recover thermodynamic landscapes and rare-event kinetics.

Biomolecular function depends on rare events and distributed ensembles. We build analysis and enhanced-sampling approaches that recover equilibrium populations, kinetic pathways and barrier-crossing rates from simulation data.

Enhanced sampling

Biasing strategies that access states and transitions beyond conventional simulation timescales.

Markov models

Network descriptions of molecular state-to-state dynamics.

DHAM methods

Dynamic histogram analysis for free energies and kinetics from biased trajectories.

Electron transfer

Rate calculations that connect electronic coupling, solvent response and molecular motion.

03

Molecular design & discovery

Translate molecular free energies into prospective design decisions.

We combine binding free energies, molecular dynamics and scalable screening to evaluate ligands, protein mutations and cooperative complexes. The goal is not only to predict a score, but to understand which interactions make a design work.

Molecular glues

Cooperativity and ternary-complex stabilisation in targeted protein degradation.

Ligand discovery

Structure-based screening and community benchmarks for challenging targets.

Mutational scans

Mechanistically guided evaluation of protein sequence space.

Computational design

Workflows that combine simulation accuracy with decision-making at scale.

Scientific workflow

Prediction grounded in mechanism.

Each project uses the level of theory and sampling strategy required by the question—not a one-size-fits-all pipeline.

01

Frame the observable

Define the experimental quantity, uncertainty and molecular hypothesis.

02

Construct the ensemble

Prepare chemically realistic states and sample the relevant conformational space.

03

Resolve the mechanism

Calculate pathways, thermodynamics, kinetics or binding cooperativity.

04

Test the prediction

Compare against experiment and use disagreement to refine the model.

Methods

Tools across electronic, atomistic and statistical scales.

QM/MMMolecular dynamicsFree-energy perturbationUmbrella samplingMarkov state modelsDHAMElectronic structureReaction-path optimisationMachine learningHigh-performance computing

Collaborate

Mechanistic hypotheses that require quantitative molecular resolution.

We collaborate on problems where multiscale simulation can discriminate reaction pathways, quantify free-energy differences or interpret kinetic observables.

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