Ligand binding to membrane proteins may be influenced significantly by the lipid membrane. In particular, the microscopic ligand concentration in the membrane compartment may exceed that in bulk solvent, resulting in overestimation of the intrinsic protein-ligand binding contribution to the apparent or measured affinity.<br/><br/>By applying the microkinetic model, the components of membrane affinity and intrinsic binding site interactions may be uncoupled to understand the relative contributions of each towards the overall measured affinity. Correction strategies will be discussed, including recent work on applying free energy calculations. These methods may guide drug discovery projects on membrane protein targets towards optimization for specific target activity and away from membrane affinity alone.

Application of the microkinetic model to uncouple specific and membrane binding at membrane protein targets

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.