Effect of different treatments of long-range interactions and sampling conditions in molecular dynamic simulations of rhodopsin embedded in a dipalmitoyl phosphatidylcholine bilayer

• The present study analyzes the effect of the simulation conditions on the results of molecular dynamics simulations of G-protein coupled receptors (GPCRs) performed with an explicit lipid bilayer. Accordingly, the present work reports the analysis of different simulations of bovine rhodopsin embedded in a dipalmitoyl phosphatidylcholine (DPPC) lipid bilayer using two different sampling conditions and two different approaches for the treatment of long-range electrostatic interactions. Specifically, sampling was carried out either by using the statistical ensembles NVT or NPT (constant number of atoms, a pressure of 1 arm in all directions and fixed temperature), and the electrostatic interactions were treated either by using a twin-cutoff, or the particle mesh Ewald summation method (PME). The results of the present study suggest that the use of the NPT ensemble in combination with the PME method provide more realistic simulations. The use of NPT during the equilibration avoids the need of an a priori estimation of the box dimensions, giving the correct area per lipid. However, once the system is equilibrated, the simulations are irrespective of the sampling conditions used. The use of an electrostatic cutoff induces artifacts on both lipid thickness and the ion distribution, but has no direct effect on the protein and water molecules.

Nyckelord

molecular dynamics

lipid bilayer

simulation setup

membrane protein

rhodopsin

electrostatics

ensembles

protein-coupled receptors

membrane-mediated interactions

particle mesh ewald

lipid-bilayers

electrostatic interactions

phospholipid-bilayers

solvated polypeptides

protonation states

force-field

computer-simulations

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