EXPERIMENTAL VALIDATION OF MOLECULAR DYNAMICS SIMULATIONS OF LIPID BILAYERS: A NEW APPROACH

¹ University of California at Irvine
² Univ. of California at Irvine

^* To whom correspondence should be addressed. E-mail: blanco{at}helium.biomol.uci.edu.

Submitted on May 28, 2004
Revised on July 22, 2004
Accepted on 18 October 2004

	Abstract

A novel protocol has been developed for comparing the structural properties of lipid bilayers determined by simulation with those determined by diffraction experiments, which makes it possible to test critically the ability of molecular dynamics (MD) simulations to reproduce experimental data. This model-independent method consists of analyzing data from MD bilayer simulations in the same way as experimental data by determining the structure factors of the system and, via Fourier reconstruction, the overall transbilayer scattering-density profiles. Multi nanosecond molecular dynamics simulations of a dioleoylphosphatidylcholine (DOPC) bilayer at 66% RH (5.4 waters/lipid) were performed in the constant pressure and temperature ensemble using the united-atom GROMACS and the all-atom CHARMM22/27 force fields with the GROMACS and NAMD software packages, respectively. The quality of the simulated bilayer structures was evaluated by comparing simulated with experimental results for bilayer thickness, area/lipid, individual molecular-component distributions, continuous and discrete structure factors, and overall scattering-density profiles. Neither the GROMACS nor the CHARMM22/27 simulations reproduced experimental data within experimental error. The widths of the simulated terminal methyl distributions showed a particularly strong disagreement with the experimentally observed distributions. A comparison of the older CHARMM22 with the newer CHARMM27 force fields shows that significant progress is being made in the development of atomic force fields for describing lipid bilayer systems empirically.

Key Words: continuous Fourier transforms, force fields, neutron diffraction, scattering-density profiles, structure factors, x-ray diffraction

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