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.

doi:10.1021/acs.jctc.8b00496

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

Journal Article · 24 September 2018 · Journal of Chemical Theory and Computation

DOI: https://doi.org/10.1021/acs.jctc.8b00496 · OSTI ID:1512613

^[1];

^[2]; Neale, Chris ^[2]; Montour, Cameron ^[3]; Ingólfsson, Helgi I. ^[1]; Di Natale, Francesco ^[4]; Lightstone, Felice C. ^[1]; Gnanakaran, S. ^[2]

Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division. Physical and Life Sciences Directorate
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Georgetown Univ., Washington, DC (United States). Biochemistry and Molecular Biology Dept.
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Applications, Simulations, and Quality Division. Computation Directorate

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. We refine the CG Martini parameters for the high- and low-melting temperature (T_m) 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.

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Research Organization:: Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Los Alamos National Laboratory (LANL)

Sponsoring Organization:: LANL Laboratory Directed Research and Development (LDRD) Program; National Inst. of Health (NIH) (United States); USDOE Office of Science (SC). Advanced Scientific Computing Research (ASCR) (SC-21)

Grant/Contract Number:: 89233218CNA000001; AC05-00OR22725; AC52-06NA25396; AC52-07NA27344

OSTI ID:: 1512613

Report Number(s):: LA-UR-18-23792; LLNL-JRNL-750994; 936287

Journal Information:: Journal of Chemical Theory and Computation, Journal Name: Journal of Chemical Theory and Computation Journal Issue: 11 Vol. 14; ISSN 1549-9618

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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