Microscopic Interactions of Melatonin, Serotonin and Tryptophan with Zwitterionic Phospholipid Membranes
The interactions at the atomic level between small molecules and the main components of cellular plasma membranes are crucial for elucidating the mechanisms allowing for the entrance of such small species inside the cell. We have performed molecular dynamics and metadynamics simulations of tryptopha...
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doaj-e8a327a3736147468de488494363e6242021-03-12T00:01:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01222842284210.3390/ijms22062842Microscopic Interactions of Melatonin, Serotonin and Tryptophan with Zwitterionic Phospholipid MembranesJordi Martí0Huixia Lu1Department of Physics, Technical University of Catalonia-Barcelona Tech, 08034 Barcelona, SpainSchool of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, ChinaThe interactions at the atomic level between small molecules and the main components of cellular plasma membranes are crucial for elucidating the mechanisms allowing for the entrance of such small species inside the cell. We have performed molecular dynamics and metadynamics simulations of tryptophan, serotonin, and melatonin at the interface of zwitterionic phospholipid bilayers. In this work, we will review recent computer simulation developments and report microscopic properties, such as the area per lipid and thickness of the membranes, atomic radial distribution functions, angular orientations, and free energy landscapes of small molecule binding to the membrane. Cholesterol affects the behaviour of the small molecules, which are mainly buried in the interfacial regions. We have observed a competition between the binding of small molecules to phospholipids and cholesterol through lipidic hydrogen-bonds. Free energy barriers that are associated to translational and orientational changes of melatonin have been found to be between 10–20 kJ/mol for distances of 1 nm between melatonin and the center of the membrane. Corresponding barriers for tryptophan and serotonin that are obtained from reversible work methods are of the order of 10 kJ/mol and reveal strong hydrogen bonding between such species and specific phospholipid sites. The diffusion of tryptophan and melatonin is of the order of 10<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mrow><mo>−</mo><mn>7</mn></mrow></msup></semantics></math></inline-formula> cm<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mn>2</mn></msup></semantics></math></inline-formula>/s for the cholesterol-free and cholesterol-rich setups.https://www.mdpi.com/1422-0067/22/6/2842melatoninserotonintryptophanphospholipid membrane |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jordi Martí Huixia Lu |
spellingShingle |
Jordi Martí Huixia Lu Microscopic Interactions of Melatonin, Serotonin and Tryptophan with Zwitterionic Phospholipid Membranes International Journal of Molecular Sciences melatonin serotonin tryptophan phospholipid membrane |
author_facet |
Jordi Martí Huixia Lu |
author_sort |
Jordi Martí |
title |
Microscopic Interactions of Melatonin, Serotonin and Tryptophan with Zwitterionic Phospholipid Membranes |
title_short |
Microscopic Interactions of Melatonin, Serotonin and Tryptophan with Zwitterionic Phospholipid Membranes |
title_full |
Microscopic Interactions of Melatonin, Serotonin and Tryptophan with Zwitterionic Phospholipid Membranes |
title_fullStr |
Microscopic Interactions of Melatonin, Serotonin and Tryptophan with Zwitterionic Phospholipid Membranes |
title_full_unstemmed |
Microscopic Interactions of Melatonin, Serotonin and Tryptophan with Zwitterionic Phospholipid Membranes |
title_sort |
microscopic interactions of melatonin, serotonin and tryptophan with zwitterionic phospholipid membranes |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-03-01 |
description |
The interactions at the atomic level between small molecules and the main components of cellular plasma membranes are crucial for elucidating the mechanisms allowing for the entrance of such small species inside the cell. We have performed molecular dynamics and metadynamics simulations of tryptophan, serotonin, and melatonin at the interface of zwitterionic phospholipid bilayers. In this work, we will review recent computer simulation developments and report microscopic properties, such as the area per lipid and thickness of the membranes, atomic radial distribution functions, angular orientations, and free energy landscapes of small molecule binding to the membrane. Cholesterol affects the behaviour of the small molecules, which are mainly buried in the interfacial regions. We have observed a competition between the binding of small molecules to phospholipids and cholesterol through lipidic hydrogen-bonds. Free energy barriers that are associated to translational and orientational changes of melatonin have been found to be between 10–20 kJ/mol for distances of 1 nm between melatonin and the center of the membrane. Corresponding barriers for tryptophan and serotonin that are obtained from reversible work methods are of the order of 10 kJ/mol and reveal strong hydrogen bonding between such species and specific phospholipid sites. The diffusion of tryptophan and melatonin is of the order of 10<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mrow><mo>−</mo><mn>7</mn></mrow></msup></semantics></math></inline-formula> cm<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mn>2</mn></msup></semantics></math></inline-formula>/s for the cholesterol-free and cholesterol-rich setups. |
topic |
melatonin serotonin tryptophan phospholipid membrane |
url |
https://www.mdpi.com/1422-0067/22/6/2842 |
work_keys_str_mv |
AT jordimarti microscopicinteractionsofmelatoninserotoninandtryptophanwithzwitterionicphospholipidmembranes AT huixialu microscopicinteractionsofmelatoninserotoninandtryptophanwithzwitterionicphospholipidmembranes |
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1724223553305313280 |