Heterogeneous dielectric generalized Born model with a van der Waals term provides improved association energetics of membrane-embedded transmembrane helices.
The heterogeneous dielectric generalized Born (HDGB) implicit membrane formalism is extended by the addition of a van der Waals dispersion term to better describe the nonpolar components of the free energy of solvation. The new model, termed HDGBvdW, improves the energy estimates in the hydrophobic interior of the membrane, where polar and charged species are rarely found and nonpolar interactions become significant. The implicit van der Waals term for the membrane environment extends the model from Gallicchio et al. (J. Comput. Chem. 2004, 25, 479) by combining separate contributions from each of the membrane components. The HDGBvdW model is validated with a series of test cases ranging from membrane insertion and pair association profiles of amino acid side chain analogs and transmembrane helices. Overall, the HDGBvdW model leads to increased agreement with explicit membrane simulation results and experimental data. © 2016 Wiley Periodicals, Inc.
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, 48824.
Bercem
B
Dutagaci
Department of Chemistry, Michigan State University, East Lansing, Michigan, 48824.
Maryam
M
Sayadi
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, 48824.
Michael
M
Feig
D002462:Cell Membrane / Q000378:metabolism*; D060833:Cellular Microenvironment; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000378:metabolism*; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D008565:Membrane Proteins; D012997:Solvents
generalized Born formalism; implicit membrane model; transmembrane helix dimers