Interaction of neurotransmitters with a phospholipid bilayer

A molecular dynamics study

Günther H. Peters, Mikkel Werge, Maria Northved Elf-Lind, Jesper M. Madsen , Gustavo Velardez, Peter Westh

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    We have performed a series of molecular dynamics simulations to study the interactions between the neurotransmitters (NTs) γ-aminobutyrate (GABA), glycine (GLY), acetylcholine (ACH) and glutamate (GLU) as well as the amidated/acetylated γ-aminobutyrate (GABAneu) and the osmolyte molecule glycerol (GOL) with a dipalmitoylphosphatidylcholine (DPPC) bilayer. In agreement with previously published experimental data, we found the lowest membrane affinity for the charged molecules and a moderate affinity for zwitterionic and polar molecules. The affinity can be ranked as follows: ACH-GLU 蠐 GABA < GLY 蠐 GABAneu蠐 GOL. The latter three penetrated the bilayer at most with the deepest location being close to the glycerol backbone of the phospholipids. Even at that position, these solutes were noticeably hydrated and carried ∼30-80% of the bulk water along. The mobility of hydration water at the solute is also affected by the penetration into the bilayer. Two time scales of exchanging water molecules could be determined. In the bulk phase, the hydration layer contains ∼20% slow exchanging water molecules which increases 2-3 times as the solutes entered the bilayer. Our results indicate that there is no intermediate exchange of slow moving water molecules from the solutes to the lipid atoms and vice versa. Instead, the exchange relies on the reservoir of unbounded ("free") water molecules in the interfacial bilayer region. Results from the equilibrium simulations are in good agreement with the results from umbrella sampling simulations, which were conducted for the four naturally occurring NTs. Free energy profiles for ACH and GLU show a minimum of ∼2-3 kJ/mol close to the bilayer interface, while for GABA and GLY, a minimum of respectively ∼2 kJ/mol and ∼5 kJ/mol is observed when these NTs are located in the vicinity of the lipid glycerol backbone. The most important interaction of NTs with the bilayer is the charged amino group of NTs with the lipid phosphate group
    OriginalsprogEngelsk
    TidsskriftChemistry and Physics of Lipids
    Vol/bind184
    Sider (fra-til)7-17
    ISSN0009-3084
    DOI
    StatusUdgivet - 2014

    Citer dette

    Peters, Günther H. ; Werge, Mikkel ; Northved Elf-Lind, Maria ; M. Madsen , Jesper ; Velardez, Gustavo ; Westh, Peter. / Interaction of neurotransmitters with a phospholipid bilayer : A molecular dynamics study. I: Chemistry and Physics of Lipids. 2014 ; Bind 184. s. 7-17.
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    title = "Interaction of neurotransmitters with a phospholipid bilayer: A molecular dynamics study",
    abstract = "We have performed a series of molecular dynamics simulations to study the interactions between the neurotransmitters (NTs) γ-aminobutyrate (GABA), glycine (GLY), acetylcholine (ACH) and glutamate (GLU) as well as the amidated/acetylated γ-aminobutyrate (GABAneu) and the osmolyte molecule glycerol (GOL) with a dipalmitoylphosphatidylcholine (DPPC) bilayer. In agreement with previously published experimental data, we found the lowest membrane affinity for the charged molecules and a moderate affinity for zwitterionic and polar molecules. The affinity can be ranked as follows: ACH-GLU 蠐 GABA < GLY 蠐 GABAneu蠐 GOL. The latter three penetrated the bilayer at most with the deepest location being close to the glycerol backbone of the phospholipids. Even at that position, these solutes were noticeably hydrated and carried ∼30-80{\%} of the bulk water along. The mobility of hydration water at the solute is also affected by the penetration into the bilayer. Two time scales of exchanging water molecules could be determined. In the bulk phase, the hydration layer contains ∼20{\%} slow exchanging water molecules which increases 2-3 times as the solutes entered the bilayer. Our results indicate that there is no intermediate exchange of slow moving water molecules from the solutes to the lipid atoms and vice versa. Instead, the exchange relies on the reservoir of unbounded ({"}free{"}) water molecules in the interfacial bilayer region. Results from the equilibrium simulations are in good agreement with the results from umbrella sampling simulations, which were conducted for the four naturally occurring NTs. Free energy profiles for ACH and GLU show a minimum of ∼2-3 kJ/mol close to the bilayer interface, while for GABA and GLY, a minimum of respectively ∼2 kJ/mol and ∼5 kJ/mol is observed when these NTs are located in the vicinity of the lipid glycerol backbone. The most important interaction of NTs with the bilayer is the charged amino group of NTs with the lipid phosphate group",
    author = "Peters, {G{\"u}nther H.} and Mikkel Werge and {Northved Elf-Lind}, Maria and {M. Madsen}, Jesper and Gustavo Velardez and Peter Westh",
    year = "2014",
    doi = "10.1016/j.chemphyslip.2014.08.003",
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    Interaction of neurotransmitters with a phospholipid bilayer : A molecular dynamics study. / Peters, Günther H.; Werge, Mikkel ; Northved Elf-Lind, Maria; M. Madsen , Jesper ; Velardez, Gustavo; Westh, Peter.

    I: Chemistry and Physics of Lipids, Bind 184, 2014, s. 7-17.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Interaction of neurotransmitters with a phospholipid bilayer

    T2 - A molecular dynamics study

    AU - Peters, Günther H.

    AU - Werge, Mikkel

    AU - Northved Elf-Lind, Maria

    AU - M. Madsen , Jesper

    AU - Velardez, Gustavo

    AU - Westh, Peter

    PY - 2014

    Y1 - 2014

    N2 - We have performed a series of molecular dynamics simulations to study the interactions between the neurotransmitters (NTs) γ-aminobutyrate (GABA), glycine (GLY), acetylcholine (ACH) and glutamate (GLU) as well as the amidated/acetylated γ-aminobutyrate (GABAneu) and the osmolyte molecule glycerol (GOL) with a dipalmitoylphosphatidylcholine (DPPC) bilayer. In agreement with previously published experimental data, we found the lowest membrane affinity for the charged molecules and a moderate affinity for zwitterionic and polar molecules. The affinity can be ranked as follows: ACH-GLU 蠐 GABA < GLY 蠐 GABAneu蠐 GOL. The latter three penetrated the bilayer at most with the deepest location being close to the glycerol backbone of the phospholipids. Even at that position, these solutes were noticeably hydrated and carried ∼30-80% of the bulk water along. The mobility of hydration water at the solute is also affected by the penetration into the bilayer. Two time scales of exchanging water molecules could be determined. In the bulk phase, the hydration layer contains ∼20% slow exchanging water molecules which increases 2-3 times as the solutes entered the bilayer. Our results indicate that there is no intermediate exchange of slow moving water molecules from the solutes to the lipid atoms and vice versa. Instead, the exchange relies on the reservoir of unbounded ("free") water molecules in the interfacial bilayer region. Results from the equilibrium simulations are in good agreement with the results from umbrella sampling simulations, which were conducted for the four naturally occurring NTs. Free energy profiles for ACH and GLU show a minimum of ∼2-3 kJ/mol close to the bilayer interface, while for GABA and GLY, a minimum of respectively ∼2 kJ/mol and ∼5 kJ/mol is observed when these NTs are located in the vicinity of the lipid glycerol backbone. The most important interaction of NTs with the bilayer is the charged amino group of NTs with the lipid phosphate group

    AB - We have performed a series of molecular dynamics simulations to study the interactions between the neurotransmitters (NTs) γ-aminobutyrate (GABA), glycine (GLY), acetylcholine (ACH) and glutamate (GLU) as well as the amidated/acetylated γ-aminobutyrate (GABAneu) and the osmolyte molecule glycerol (GOL) with a dipalmitoylphosphatidylcholine (DPPC) bilayer. In agreement with previously published experimental data, we found the lowest membrane affinity for the charged molecules and a moderate affinity for zwitterionic and polar molecules. The affinity can be ranked as follows: ACH-GLU 蠐 GABA < GLY 蠐 GABAneu蠐 GOL. The latter three penetrated the bilayer at most with the deepest location being close to the glycerol backbone of the phospholipids. Even at that position, these solutes were noticeably hydrated and carried ∼30-80% of the bulk water along. The mobility of hydration water at the solute is also affected by the penetration into the bilayer. Two time scales of exchanging water molecules could be determined. In the bulk phase, the hydration layer contains ∼20% slow exchanging water molecules which increases 2-3 times as the solutes entered the bilayer. Our results indicate that there is no intermediate exchange of slow moving water molecules from the solutes to the lipid atoms and vice versa. Instead, the exchange relies on the reservoir of unbounded ("free") water molecules in the interfacial bilayer region. Results from the equilibrium simulations are in good agreement with the results from umbrella sampling simulations, which were conducted for the four naturally occurring NTs. Free energy profiles for ACH and GLU show a minimum of ∼2-3 kJ/mol close to the bilayer interface, while for GABA and GLY, a minimum of respectively ∼2 kJ/mol and ∼5 kJ/mol is observed when these NTs are located in the vicinity of the lipid glycerol backbone. The most important interaction of NTs with the bilayer is the charged amino group of NTs with the lipid phosphate group

    U2 - 10.1016/j.chemphyslip.2014.08.003

    DO - 10.1016/j.chemphyslip.2014.08.003

    M3 - Journal article

    VL - 184

    SP - 7

    EP - 17

    JO - Chemistry and Physics of Lipids

    JF - Chemistry and Physics of Lipids

    SN - 0009-3084

    ER -