Atomistic framework estimates how a peripheral protein binds membranes, matching experiment for a bacterial phospholipase
- The authors describe a statistical-mechanical, potential-of-mean-force-based route for quantifying how dilute peripheral membrane proteins bind homogeneous lipid membranes.
- Well-tempered metadynamics and extended adaptive biasing force were used to sample the many noncovalent contacts involved, including cation–π and hydrophobic interactions.
- Applied to a bacterial phosphatidylinositol-specific phospholipase C on phosphatidylcholine membranes, the computed standard binding free energy agreed closely with experimental estimates.
💡 Points Based on the abstract
One protein on one homogeneous PC bilayer is a friendly test case. Real membranes are anionic, mixed and curved, and metadynamics/ABF convergence there gets much harder. If I wanted this for a peripheral target, I'd first check that the standard-state correction and the orientation/collective-variable choice hold up, and that the result isn't sensitive to the force field's cation-pi and lipid parameters. Agreement to experiment on a single system could still be partly fortuitous.