Lipid14: The Amber Lipid Force Field

Abstract

The AMBER lipid force field has been updated to create Lipid14, allowing tensionless simulation of a number of lipid types with the AMBER MD package. The modular nature of this force field allows numerous combinations of head and tail groups to create different lipid types, enabling the easy insertion of new lipid species. The Lennard-Jones and torsion parameters of both the head and tail groups have been revised and updated partial charges calculated. The force field has been validated by simulating bilayers of six different lipid types for a total of 0.5 μs each without applying a surface tension; with favorable comparison to experiment for properties such as area per lipid, volume per lipid, bilayer thickness, NMR order parameters, scattering data, and lipid lateral diffusion. As the derivation of this force field is consistent with the AMBER development philosophy, Lipid14 is compatible with the AMBER protein, nucleic acid, carbohydrate, and small molecule force fields.

Figure 1

A box of 144 pentadecane molecules simulated in the NPT ensemble at 298.15 K using the General Amber Force Field to model the carbon chains.

Figure 2

The energy profile for rotating about selected torsions of a cis-5-decene molecule. Energy evaluated using QM and the HM-IE method (filled triangle ▲), AMBER with standard GAFF parameters (dotted line), and AMBER with Lipid14 parameters (black line). Torsion fits from the top are as follows: CH₂–CH–CH–CH₂, CH–CH–CH₂–CH₂, and CH–CH₂–CH₂–CH₂.

Figure 3

Structure and charges of Lipid11/Lipid14 headgroup and tail group caps.

Figure 4

A capped lauroyl tail group residue was used to fit the oS-cC-cD-cD and oC-cC-cD-cD torsions.

Figure 5

The energy profiles for rotating about selected torsions of a capped lauroyl tail group residue. Energy evaluated using QM and the HM-IE method (filled triangle ▲), AMBER with standard GAFF/Lipid11 parameters (dotted line), and AMBER with Lipid14 parameters (black line). Torsion fits from the top are oC-cC-cD-cD and oS-cC-cD-cD.

Figure 6

Calculated ¹³C NMR T₁ relaxation times for selected alkane chains and comparison to experiment. Values at 312 K.

Figure 7

Simulation NMR order parameters for the six lipid systems and comparison to experiment.^,,−

Figure 8

The total and decomposed electron density profiles for each of the six lipid bilayer systems with contributions from water, choline (CHOL), phosphate (PO₄), glycerol (GLY), carbonyl (COO), methylene (CH₂), unsaturated CH=CH and terminal methyls (CH₃).

Figure 9

Simulation X-ray scattering form factors for the six lipid systems (black line) and comparison to experiment^,,,, (cyan circles). Inset: Simulation neutron scattering form factors at 100% D₂O (black line), 70% D₂O (red line), and 50% D₂O (blue line) and comparison to experiment^, (black, red, and blue circles, respectively).

Figure 10

Plot of ΔD_B-_H versus area per lipid A_L for the three all-atom lipid force fields CHARMM36 (squares), Slipids (diamonds), and AMBER Lipid14 (circles). Values shown for DLPC (green), DMPC (magenta), DPPC (blue), DOPC (red), and POPC (orange).

Figure 11

Time averaged mean square displacement of the center of mass of the lipid molecules versus NVE simulation time.

Figure 12

Lateral diffusion coefficients for the six lipid types calculated using different time ranges of the mean square displacement curve for the linear fit.