HDGB Implicit Membrane Model with a van Der Waals Dispersion Term

Abstract

The Heterogeneous Dielectric Generalized Born (HDGB) model(1) allows simulations of membrane-bound systems with an implicit membrane formalism using dielectric profiles matched against explicit membrane simulations. In this study, an extension of the original model is described where the solvent-accessible surface area term is extended with a van der Waals dispersion term to improve the estimation of the non-polar components of the free energy of solvation. This is especially important in the hydrophobic region of bilayer systems where charged and polar groups are rarely interacting. The dispersion term was modeled after the AGBNP method originally introduced by Gallicchio et al.(2) but extended to the membrane environment via atom-type dependent density profiles along the membrane normal. The model was initially parametrized against membrane insertion free energy profiles of amino acid analogs from explicit lipid simulations. Further validation involved the energetics of model compound interactions and peptide-peptide interactions within the membrane.[1] Tanizaki, S. et al. 2005, J. Chem. Phys. 122, 124706.[2] Gallicchio, E. et al. 2004, J Comput. Chem. 25, 479-499.