Amino Acid Insertion Energetics in a POPC Bilayer from Unbiased Molecular Dynamics (opens in new tab)

Membrane association is governed by the thermodynamics of amino acid partitioning between water and the lipid bilayer. Here, we quantified amino acid side-chain insertion energetics in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer using unbiased molecular dynamics simulations. Equilibrium depth distributions of 28 analogs, including multiple protonation states, were converted into potentials of mean force (PMFs) by Boltzmann inversion. The resulting PMFs reproduced the mai...