Enhanced Sampling of Phase Transitions in Coarse-Grained Lipid Bilayers.

ABSTRACT

Freezing and melting of dipalmitoylphosphatidylcholine (DPPC) bilayers are simulated in both the explicit (Wet) and implicit solvent (Dry) coarse-grained MARTINI force fields with enhanced sampling, via the isobaric, molecular dynamics version of the generalized replica exchange method (gREM). Phase transitions are described with the entropic viewpoint, based upon the statistical temperature as a function of enthalpy, TS(H) = 1/(dS(H)/dH), where S is the configurational entropy. Bilayer thickness, area per lipid, and the second-rank order parameter (P2) are calculated vs temperature in the transition range. In a 32-lipid Wet MARTINI system, transitions in the lipid and water subsystems are strongly coupled, giving rise to considerable structure in TS(H) and the need to specify the state of the water when reporting a lipid transition temperature. For gel lipid + liquid water → fluid lipid + liquid water, we find 292.4 K. The small system is influenced by finite-size effects, but it is argued that the entropic approach is well suited to revealing them, which will be particularly relevant for studies of finite nanosystems where there is no thermodynamic limit. In a 390-lipid Dry MARTINI system, two-dimensional analogues of the topographies of coexisting states ("subphases") seen in pure fluids are found. They are not seen in the 32-lipid Wet or Dry system, but the Dry lipids show a new type of state with gel in one leaflet and tilted gel in the other. Dry bilayer transition temperatures are 333.3 K (390 lipids) and 338 K (32 lipids), indicating that the 32-lipid system is not too small for a qualitative study of the transition. Physical arguments are given for Dry lipid system size dependence and for the difference between Wet and Dry systems.