Abstract
Thermodynamics of the permeation of amino acids from water to lipid bilayers is an important first step for understanding the mechanism of cell-permeating peptides and the thermodynamics of membrane protein structure and stability. In this work, we employed bias-exchange metadynamics simulations to simulate the membrane permeation of all 20 amino acids from water to the center of a dipalmitoylphosphatidylcholine (DPPC) membrane (consists of 256 lipids) by using both directional and torsion angles for conformational sampling. The overall accuracy for the free energy profiles obtained is supported by significant correlation coefficients (correlation coefficient at 0.5–0.6) between our results and previous experimental or computational studies. The free energy profiles indicated that (1) polar amino acids have larger free energy barriers than nonpolar amino acids; (2) negatively charged amino acids are the most difficult to enter into the membrane; and (3) conformational transitions for many amino acids during membrane crossing is the key for reduced free energy barriers. These results represent the first set of simulated free energy profiles of membrane crossing for all 20 amino acids.
Highlights
One of the key molecular interactions in living organisms is the interaction between amino acids and lipid bilayers of cell membranes
Lipid bilayers consist of amphipathic phospholipids that are self-assembled with long hydrophobic tails buried in the center and hydrophilic heads facing the intracellular and extracellular water environment
We further examined the convergence of free energy profiles (FEP) for 20 amino acids by comparing the profiles calculated from different simulation lengths
Summary
One of the key molecular interactions in living organisms is the interaction between amino acids and lipid bilayers of cell membranes. McDonald and Fleming performed mutations of alanine to aromatic residues in the outer membrane protein phospholipase A (OmpLA) and demonstrated the dependence of transfer free energy of aromatic side chains on the depth inside the membrane [10] Consistent with their partitioning coefficients, direct measurement of permeability of membranes to amino acids indicated that hydrophobic amino acids are much more permeable than hydrophilic ones [11]. It has successfully found that the conformational transition of aspirin [25] plays an important role for accurate estimate of transfer free energy To our knowledge, this is the first systematic study for membrane permeation of all 20 amino acids. Correlation analysis between free energy cost of permeation and physico-chemical properties of amino acids suggest hydrophobicity as the main driving force of cell permeation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
