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

Abstract

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.

Authors+Show Affiliations

Randall Centre for Cell and Molecular Biology , King's College London , London SE1 1UL , U.K.Randall Centre for Cell and Molecular Biology , King's College London , London SE1 1UL , U.K.Randall Centre for Cell and Molecular Biology , King's College London , London SE1 1UL , U.K.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31433640

Citation

Marzuoli, Irene, et al. "Lipid Head Group Parameterization for GROMOS 54A8: a Consistent Approach With Protein Force Field Description." Journal of Chemical Theory and Computation, 2019.
Marzuoli I, Margreitter C, Fraternali F. Lipid Head Group Parameterization for GROMOS 54A8: A Consistent Approach with Protein Force Field Description. J Chem Theory Comput. 2019.
Marzuoli, I., Margreitter, C., & Fraternali, F. (2019). Lipid Head Group Parameterization for GROMOS 54A8: A Consistent Approach with Protein Force Field Description. Journal of Chemical Theory and Computation, doi:10.1021/acs.jctc.9b00509.
Marzuoli I, Margreitter C, Fraternali F. Lipid Head Group Parameterization for GROMOS 54A8: a Consistent Approach With Protein Force Field Description. J Chem Theory Comput. 2019 Sep 9; PubMed PMID: 31433640.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lipid Head Group Parameterization for GROMOS 54A8: A Consistent Approach with Protein Force Field Description. AU - Marzuoli,Irene, AU - Margreitter,Christian, AU - Fraternali,Franca, Y1 - 2019/09/09/ PY - 2019/8/23/pubmed PY - 2019/8/23/medline PY - 2019/8/22/entrez JF - Journal of chemical theory and computation JO - J Chem Theory Comput N2 - 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. SN - 1549-9626 UR - https://www.unboundmedicine.com/medline/citation/31433640/Lipid_head_group_parameterisation_for_GROMOS_54a8:_a_consistent_approach_with_protein_force_field_description DB - PRIME DP - Unbound Medicine ER -
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