Capturing Phase Behavior of Ternary Lipid Mixtures with a Refined Martini Coarse-Grained Force Field

• DOI: 10.1021/acs.jctc.8b00496
• Publication Date: 2018-09-25T21:35:35Z
• Authors: Timothy S. Carpenter; Cesar A. López; Chris Neale; Cameron Montour; Helgi I. Ingólfsson; Francesco Di Natale; Felice C. Lightstone; S. Gnanakaran
• Keywords: Force Field; Lipid microdomain

Whether lipid rafts are present in the membranes of living cells remains hotly disputed despite their incontrovertible existence liposomes at 298 K. In attempts to resolve this debate, molecular dynamics (MD) simulations have been extensively used study phase separation high resolution. However, computation has limited utility respect because experimental distributions phases lamellar mixtures poorly reproduced by simulations. particular, all-atom (AA) approaches suffer from restrictions on accessible time scales and system sizes whereas more efficient coarse-grained (CG) force fields remain insufficiently accurate achieve correspondence with experiment. work, we refine CG Martini parameters for high- low-melting temperature ( Tm) lipids 1,2-dipalmitoyl- sn-glycero-3-phosphatidylcholine (DPPC) 1,2-dioleoyl- (DOPC). Our approach involves modification bonded based fitting atomistic conducted CHARMM36 field. The resulting reproduce structural thermodynamic properties homogeneous while concurrently improving simulation fidelity diagrams DPPC, DOPC, cholesterol mixtures. Importantly, refined provide much better accuracy regions near critical point that mimic concentrations under physiological conditions.