Mutated G Proteins and GPCRs
Our research on G protein coupled receptors (GPCRs) focuses on understanding how naturally occurring or disease-associated mutations alter ligand binding, receptor activation, and signaling outcomes. We combine free energy perturbation (FEP), molecular dynamics simulations, and structural modeling to explain mutational effects at the molecular level.
This research line supports rational design of ligands tailored to specific receptor variants, informs on mechanisms of altered drug response, and advances mutation-aware GPCR pharmacology.
Molecular Determinants of GPCR Mutation Effects
We investigate how individual amino acid substitutions influence receptor–ligand free energies, structural rearrangements, and functional signaling outcomes. By integrating simulation data and structural analysis, we identify the molecular interactions that drive mutation-induced changes in ligand affinity and receptor function.
Computational Framework
Our mutation studies integrate:
- QresFEP for quantitative mutation free energy predictions
- Molecular dynamics to understand dynamic and structural effects
- Comparative structural analysis to identify mutation hotspots
- Ligand design workflows for variant-specific optimisation
These approaches allow us to establish molecular rules governing GPCR mutational effects and apply them to drug discovery pipelines.