title: Biomembrane simulations of 12 lipid types using the general amber force field in a tensionless ensemble.
abstract: The AMBER family of force fields is one of the most commonly used alternatives to describe proteins and drug-like molecules in molecular dynamics simulations. However, the absence of a specific set of parameters for lipids has been limiting the widespread application of this force field in biomembrane simulations, including membrane protein simulations and drug-membrane simulations. Here, we report the systematic parameterization of 12 common lipid types consistent with the General Amber Force Field (GAFF), with charge-parameters determined with RESP at the HF/6-31G(d) level of theory, to be consistent with AMBER. The accuracy of the scheme was evaluated by comparing predicted and experimental values for structural lipid properties in MD simulations in an NPT ensemble with explicit solvent in 100:100 bilayer systems. Globally, a consistent agreement with experimental reference data on membrane structures was achieved for some lipid types when using the typical MD conditions normally employed when handling membrane proteins and drug-membrane simulations (a tensionless NPT ensemble, 310 K), without the application of any of the constraints often used in other biomembrane simulations (such as the surface tension and the total simulation box area). The present set of parameters and the universal approach used in the parameterization of all the lipid types described here, as well as the consistency with the AMBER force field family, together with the tensionless NPT ensemble used, opens the door to systematic studies combining lipid components with small drug-like molecules or membrane proteins and show the potential of GAFF in dealing with biomembranes.
authors.affiliation: a REQUIMTE, Departamento de Química e Bioquímica , Faculdade de Ciências, Universidade do Porto , Rua do Campo Alegre s/n, 4169-007 , Porto , Portugal .
authors.forename: João T S
authors.initials: JT
authors.lastname: Coimbra
authors.forename: Sérgio F
authors.initials: SF
authors.lastname: Sousa
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Fernandes
authors.forename: Maria
authors.initials: M
authors.lastname: Rangel
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ramos
mesh_terms: D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines