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

Timothy S. Carpenter, Cesar A. López, Chris Neale, Cameron Montour, Helgi I. Ingólfsson, Francesco Di Natale, Felice C Lightstone, S. Gnanakaran

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
JournalJournal of Chemical Theory and Computation
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Phase behavior
Lipids
field theory (physics)
lipids
Phosphatidylcholines
simulation
melting
membranes
Liposomes
rafts
Cholesterol
Membrane Lipids
cholesterol
Phase separation
Phase diagrams
Melting point
Molecular dynamics
Structural properties
Melting
Thermodynamic properties

ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry

Cite this

Carpenter, T. S., López, C. A., Neale, C., Montour, C., Ingólfsson, H. I., Di Natale, F., ... Gnanakaran, S. (Accepted/In press). Capturing Phase Behavior of Ternary Lipid Mixtures with a Refined Martini Coarse-Grained Force Field. Journal of Chemical Theory and Computation. https://doi.org/10.1021/acs.jctc.8b00496

Capturing Phase Behavior of Ternary Lipid Mixtures with a Refined Martini Coarse-Grained Force Field. / Carpenter, Timothy S.; López, Cesar A.; Neale, Chris; Montour, Cameron; Ingólfsson, Helgi I.; Di Natale, Francesco; Lightstone, Felice C; Gnanakaran, S.

In: Journal of Chemical Theory and Computation, 01.01.2018.

Research output: Contribution to journalArticle

Carpenter, Timothy S. ; López, Cesar A. ; Neale, Chris ; Montour, Cameron ; Ingólfsson, Helgi I. ; Di Natale, Francesco ; Lightstone, Felice C ; Gnanakaran, S. / Capturing Phase Behavior of Ternary Lipid Mixtures with a Refined Martini Coarse-Grained Force Field. In: Journal of Chemical Theory and Computation. 2018.
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