Protocol and Validation of CHARMM-GUI Hex Phase Builder

Abstract

It is becoming increasingly apparent that protein dynamics, conformation, and therefore, function are dependent on the stresses within the bilayer – one of which being bending frustration. The amount of bending frustration is dependent on the bending modulus (kc) and spontaneous radius of curvature (R0–1) for a given lipid composition. These quantities are difficult to obtain computationally, particularly by all-atom molecular dynamics (MD) simulation. For many years, experimentalists (and much more recently, simulators) have used the lipid hexagonal phase to obtain these quantities. The inverse lipid hexagonal phase exists in high temperature and low water domains of the certain lipid's phase diagram. In this phase, lipids aggregate with their hydrophilic heads oriented along hexagonally packed water pores. Although this phase spontaneously assembles, the equilibration time necessary for this type of process is unfeasible for typical all-atom MD simulations. Here, a simple and reproducible methodology, Hex Phase Builder, is described and validated as an integrated part of the CHARMM-GUI framework (http://www.charmm-gui.org/input/hexphase). By calculating the pressure within the water pore, kc and R0–1 can be obtained for any lipid composition. This sensitive technique provides energetic insight into lipid systems and allows for further validation of the oft-used CHARMM C36 lipid force field.