Assessing atomistic and coarse-grained force fields for protein-lipid interactions: The formidable challenge of an ionizable side chain in a membrane

Vorobyov, I, Li, L and Allen, T 2008, 'Assessing atomistic and coarse-grained force fields for protein-lipid interactions: The formidable challenge of an ionizable side chain in a membrane', The Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical, vol. 112, no. 32, pp. 9588-9602.


Document type: Journal Article
Collection: Journal Articles

Title Assessing atomistic and coarse-grained force fields for protein-lipid interactions: The formidable challenge of an ionizable side chain in a membrane
Author(s) Vorobyov, I
Li, L
Allen, T
Year 2008
Journal name The Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical
Volume number 112
Issue number 32
Start page 9588
End page 9602
Total pages 15
Publisher American Chemical Society
Abstract Ionizable amino acid side chains play important roles in membrane protein structure and function, including the activation of voltage-gated ion channels, where it has been previously suggested that charged side chains may move through the hydrocarbon core of the membrane. However, all-atom molecular dynamics simulations have demonstrated large free energy barriers for such lipid-exposed motions. These simulations have also revealed that the membrane will deform due to the presence of a charged side chain, leading to a complex solvation microenvironment for which empirical force fields were not specifically parametrized. We have tested the ability of the all-atom CHARMM, Drude polarizable CHARMM, and a recent implementation of a coarse-grained force field to measure the thermodynamics of arginine-membrane interactions as a function of protonation state. We have employed model systems to attempt to match experimental bulk partitioning and quantum mechanical interactions within the membrane and found that free energy profiles from nonpolarizable and polarizable CHARMM simulations are accurate to within 1-2 kcal/mol. In contrast, the coarse-grained simulations failed to reproduce the same membrane deformations, exhibit interactions that are an order of magnitude too small, and thus, have incorrect free energy profiles. These results illustrate the need for careful parametrization of coarse-grained force fields and demonstrate the utility of atomistic molecular dynamics for providing quantitative thermodynamic and mechanistic analysis of protein-lipid interactions.
Subject Physical Chemistry not elsewhere classified
DOI - identifier 10.1021/jp711492h
Copyright notice © 2008 American Chemical Society
ISSN 1520-6106
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