Critical Comparison of Biomembrane Force Fields: Protein–Lipid Interactions at the Membrane Interface

• Published in: Journal of chemical theory and computation Vol. 13; no. 5; pp. 2310 - 2321
• Main Authors: Sandoval-Perez, Angelica, Pluhackova, Kristyna, Böckmann, Rainer A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 09.05.2017
• Subjects: Animals; Aquaporins - chemistry; Aquaporins - metabolism; Bacterial Outer Membrane Proteins - chemistry; Bacterial Outer Membrane Proteins - metabolism; Biological activity; Cattle; Escherichia coli - chemistry; Escherichia coli - metabolism; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Eye Proteins - chemistry; Eye Proteins - metabolism; Hydrolases - chemistry; Hydrolases - metabolism; Insertion; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Lipids; Membrane Lipids - chemistry; Membrane Lipids - metabolism; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Molecular chains; Molecular dynamics; Molecular Dynamics Simulation; Nucleic acids; Organic chemistry; Parameterization; Parameters; Peptides; Protein Structure, Secondary; Proteins; Temporal resolution; Thermodynamics; Water - chemistry; Water - metabolism; Water conservation
• ISSN: 1549-9618; 1549-9626
• DOI: 10.1021/acs.jctc.7b00001

Molecular dynamics (MD) simulations offer the possibility to study biological processes at high spatial and temporal resolution often not reachable by experiments. Corresponding biomolecular force field parameters have been developed for a wide variety of molecules ranging from inorganic ligands and small organic molecules over proteins and lipids to nucleic acids. Force fields have typically been parametrized and validated on thermodynamic observables and structural characteristics of individual compounds, e.g. of soluble proteins or lipid bilayers. Less strictly, due to the added complexity and missing experimental data to compare to, force fields have hardly been tested on the properties of mixed systems, e.g. on protein–lipid systems. Their selection and combination for mixed systems is further complicated by the partially differing parametrization strategies. Additionally, the presence of other compounds in the system may shift the subtle balance of force field parameters. Here, we assessed the protein–lipid interactions as described in the four atomistic force fields GROMOS54a7, CHARMM36 and the two force field combinations Amber14sb/Slipids and Amber14sb/Lipid14. Four observables were compared, focusing on the membrane-water interface: the conservation of the secondary structure of transmembrane proteins, the positioning of transmembrane peptides relative to the lipid bilayer, the insertion depth of side chains of unfolded peptides absorbed at the membrane interface, and the ability to reproduce experimental insertion energies of Wimley-White peptides at the membrane interface. Significant differences between the force fields were observed that affect e.g. membrane insertion depths and tilting of transmembrane peptides.