Modification of the CHARMM force field for DMPC lipid bilayer

Abstract

The CHARMM force field for DMPC lipids was modified in order to improve agreement with experiment for a number of important properties of hydrated lipid bilayer. The modification consists in introduction of a scaling factor 0.83 for 1-4 electrostatic interactions (between atoms separated by three covalent bonds), which provides correct transgauche ratio in the alkane tails, and recalculation of the headgroup charges on the basis of HF/6-311(d,p) ab-initio computations. Both rigid TIP3P and flexible SPC water models were used with the new lipid model, showing similar results. The new model in a 75 ns simulation has shown a correct value of the area per lipid at zero surface tension, as well as good agreement with the experiment for the electron density, structure factor, and order parameters, including those in the headgroup part of lipids.

Systematic coarse-graining of molecular models by the Newton inversion method

“…In the subsequent development, the effective potentials derived in work 14 were re-parameterized after re-computation of CG site-site RDFs according to the recent modification of the CHARMM27 force field described in ref. 42. This modification of the CHARMM force field has been done with the primary aim to improve agreement with experiments for atomistic simulations of lipid bilayers, and to reproduce correctly the average area per lipid in particular.…”

M.DynaMix Studies of Solvation, Solubility and Permeability

“…The correction included two changes: 1) scaling of the socalled 1-4 electrostatic interactions (of atoms separated by exact 3 covalent bonds) was introduced, which was tuned to reproduce experimentally measured ration of trans-and gauche conformations in hydrocarbon chains, and 2) partial atom charges in the lipid headgroup were recalculated from high-quality ab-initio calculations. It was demonstrated in paper (Högberg et al, 2008) that these modifications of the CHARMM force field allowed to obtain, in 100 ns constant-pressure simulations, excellent agreement with experimentally measured properties of DMPC bilayer such as area per lipid at zero tension, electron density, structure factor and order parameters. An important feature of these simulations was also that long-range correction to the Lennard-Jones potential was included into pressure calculations.…”

“…For example, the CHARMM force field favour to rigid gel-like structures of bilayers composed of saturated lipids, and in order to keep bilayer in a natural liquid crystalline phase one need to apply surface tension (Lyubartsev & Rabinovich, 2011: and references therein). In paper (Högberg et al, 2008) a solution was suggested how to improve the CHARMM force field in order to simulate DMPC lipid bilayer in constantpressure tensionless simulations. The correction included two changes: 1) scaling of the socalled 1-4 electrostatic interactions (of atoms separated by exact 3 covalent bonds) was introduced, which was tuned to reproduce experimentally measured ration of trans-and gauche conformations in hydrocarbon chains, and 2) partial atom charges in the lipid headgroup were recalculated from high-quality ab-initio calculations.…”

“…In continuation of paper (Högberg et al, 2008), the modified CHARMM force field was used to simulate bilayers consisting of two similar lipids: DSPC (which differ from DMPC lipid displayed in Figure 13 that it contains 18 carbon atoms in each tail) and DOPC lipid (which exactly as DSPC contains 18 carbon atoms in each tail but have a double bond between 9-th and 10-th carbons in the second tail). Despite very similar chemical structure, bilayers composed of these lipids show different behaviour, and have noticeably different temperatures of the gel -liquid crystalline transition: 24 o C for DMPC, 53 o C for DSPC, and 5 o C for DOPC, that is why in the physiological range of temperatures DMPC and DOPC bilayers exist in a liquid crystalline phase while DSPC is in a gel phase.…”

Ethanol enhances collective dynamics of lipid membranes

“…Long-range electrostatic forces were taken into account using the particle mesh Ewald (PME) approach [24]. The lipids were described by all-atom, empirical force fields proposed by Hogberg et al [25], the water molecules by the TIP3P model [26], and the ethanol force field was taken from [27]. The connection between the MD trajectories and the inelastic neutron data is via the density correlation function.…”