Position-resolved free energy of solvation for amino acids in lipid membranes from molecular dynamics simulations.
Studies of insertion and interactions of amino acids in lipid membranes are pivotal to our understanding of membrane protein structure and function. Calculating the insertion cost as a function of transmembrane helix sequence is thus an important step towards improved membrane protein prediction and eventually drug design. Here, we present position-dependent free energies of solvation for all amino acid analogs along the membrane normal. The profiles cover the entire region from bulk water to hydrophobic core, and were produced from all-atom molecular dynamics simulations. Experimental differences corresponding to mutations and costs for entire segments match experimental data well, and in addition the profiles provide the spatial resolution currently not available from experiments. Polar side-chains largely maintain their hydration and assume quite ordered conformations, which indicates the solvation cost is mainly entropic. The cost of solvating charged side-chains is not only significantly lower than for implicit solvation models, but also close to experiments, meaning these could well maintain their protonation states inside the membrane. The single notable exception to the experimental agreement is proline, which is quite expensive to introduce in vivo despite its hydrophobicity--a difference possibly explained by kinks making it harder to insert helices in the translocon.
Johansson
Anna C V
AC
Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden.
Lindahl
Erik
E
D000596:Amino Acids / Q000737:chemistry*; D003198:Computer Simulation; D008051:Lipid Bilayers; D008565:Membrane Proteins; D008958:Models, Molecular; D009038:Motion; D012995:Solubility; D013816:Thermodynamics
D000596:Amino Acids; D008051:Lipid Bilayers; D008565:Membrane Proteins