Lipid Head Group Parameterization for GROMOS 54A8: A Consistent Approach with Protein Force Field Description

[Image: see text] Membranes are a crucial component of both bacterial and mammalian cells, being involved in signaling, transport, and compartmentalization. This versatility requires a variety of lipid species to tailor the membrane’s behavior as needed, increasing the complexity of the system. Molecular dynamics simulations have been successfully applied to study model membranes and their interactions with proteins, elucidating some crucial mechanisms at the atomistic detail and thus complementing experimental techniques. An accurate description of the functional interplay of the diverse membrane components crucially depends on the selected parameters that define the adopted force field. A coherent parameterization for lipids and proteins is therefore needed. In this work, we propose and validate new lipid head group parameters for the GROMOS 54A8 force field, making use of recently published parametrizations for key chemical moieties present in lipids. We make use additionally of a new canonical set of partial charges for lipids, chosen to be consistent with the parameterization of soluble molecules such as proteins. We test the derived parameters on five phosphocholine model bilayers, composed of lipid patches four times larger than the ones used in previous studies, and run 500 ns long simulations of each system. Reproduction of experimental data like area per lipid and deuterium order parameters is good and comparable with previous parameterizations, as well as the description of liquid crystal to gel-phase transition. On the other hand, the orientational behavior of the head groups is more realistic for this new parameter set, and this can be crucial in the description of interactions with other polar molecules. For that reason, we tested the interaction of the antimicrobial peptide lactoferricin with two model membranes showing that the new parameters lead to a weaker peptide–membrane binding and give a more realistic outcome in comparing binding to antimicrobial versus mammal membranes.