LIPID11: A Modular Framework for Lipid Simulations Using Amber

Abstract

Accurate simulation of complex lipid bilayers has long been a goal in condensed phase molecular dynamics (MD). Structure and function of membrane-bound proteins are highly dependent on the lipid bilayer environment and are challenging to study through experimental methods. Within Amber, there has been limited focus on lipid simulations, although some success has been seen with the use of the General Amber Force Field (GAFF). However, to date there are no dedicated Amber lipid force fields. In this paper we describe a new charge derivation strategy for lipids consistent with the Amber RESP approach, and a new atom and residue naming and type convention. In the first instance, we have combined this approach with GAFF parameters. The result is LIPID11, a flexible, modular framework for the simulation of lipids that is fully compatible with the existing Amber force fields. The charge derivation procedure, capping strategy and nomenclature for LIPID11, along with preliminary simulation results and a discussion of the planned long-term parameter development are presented here. Our findings suggest that Lipid11 is a modular framework feasible for phospholipids and a flexible starting point for the development of a comprehensive, Amber-compatible lipid force field.

Phosphatidylcholine reverse micelles on the wrong track in molecular dynamics simulations of phospholipids in an organic solvent

“…56 Additionally, initial versions of General Amber Force Field (GAFF) and Amber lipid force fields were also unable to reproduce the experimental area per lipid in a tensionless ensemble. [57][58][59] In these two closely related parametrizations, the problem was later remedied by refitting torsional and LJ parameters of the hydrocarbon tails 60,61 against bulk pentadecane.…”

A Barley Efflux Transporter Operates in a Na+-Dependent Manner, as Revealed by a Multidisciplinary Platform

“…Lipids and explicit water and salt molecules were added to produce a system with 102,070 atoms that was minimized by AMBER. The force field algorithms during modeling were ff99SB (Hornak et al, 2006) for protein, lipid11 (Skjevik et al, 2012) for lipid, and TIP3 (Jorgensen et al, 1983) for water molecules. After gradually heating the system to 300K, equilibration MD in duration of 30 ns and production runs of 84 ns were performed, using the SHAKE algorithm with a time step of 2 fs and Langevin dynamics (LD) with the collision frequency of 1.0, a random seed, and surface tension of 10.0 dyne/cm.…”

“…This ensured that initial configurations of lipid/salt/water in all variants remained identical for all MD simulations. During MD simulations, a 574-residue protein was embedded in an aqueous DOPC lipid bilayer, and the ff99SB (Hornak et al, 2006) and lipid11 (Skjevik et al, 2012) force fields were applied to parametrize the protein and lipid components, respectively. Along with the explicit TIP3 (Jorgensen et al, 1983) water molecules, ;102,000 atoms of models were minimized using 1000 cycles of steepest descent and conjugate gradients.…”

Predicting peptide vaccine candidates against H1N1 influenza virus through theoretical approaches

“…Then, these files were converted into files that conform to the Lipid11 naming convention using charmmlipid2amber.x script included in the AMBER 12 package [42]. Lipid11 is the Amber lipid force field that includes parameters from the general amber force field (GAFF) [43,44]. The topologies for the pMHC-II complexes were constructed by the Leap module using the ff99SB and Lipid11 force field [42,43].…”

“…Lipid11 is the Amber lipid force field that includes parameters from the general amber force field (GAFF) [43,44]. The topologies for the pMHC-II complexes were constructed by the Leap module using the ff99SB and Lipid11 force field [42,43]. Then, these structures were minimized and heated with sander by the following three steps.…”