Similarities and differences of serotonin and its precursors in their interactions with model membranes studied by molecular dynamics simulation

Wood, Irene; Martini, M. Florencia; Pickholz, Mónica

doi:10.1016/j.molstruc.2013.04.011

Cited by 18 publications

(15 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Broadness of the 5-HT profile demonstrates its relative mobility at the bilayer interface, which is in relation with negative PMF values in the corresponding zone. These results are in agreement with recent studies describing a similar location of 5-HT in POPC and DOPC membranes (32,56).…”

Section: Serotonin Interacts With Lipid Bilayers At the Interfacesupporting

confidence: 93%

Antioxidant and Membrane Binding Properties of Serotonin Protect Lipids from Oxidation

Azouzi

Santuz

Morandat

et al. 2017

Biophysical Journal

View full text Add to dashboard Cite

Serotonin (5-hydroxytryptamine, 5-HT) is a well-known neurotransmitter that is involved in a growing number of functions in peripheral tissues. Recent studies have shown nonpharmacological functions of 5-HT linked to its chemical properties. Indeed, it was reported that 5-HT may, on the one hand, bind lipid membranes and, on the other hand, protect red blood cells through a mechanism independent of its specific receptors. To better understand these underevaluated properties of 5-HT, we combined biochemical, biophysical, and molecular dynamics simulations approaches to characterize, at the molecular level, the antioxidant capacity of 5-HT and its interaction with lipid membranes. To do so, 5-HT was added to red blood cells and lipid membranes bearing different degrees of unsaturation. Our results demonstrate that 5-HT acts as a potent antioxidant and binds with a superior affinity to lipids with unsaturation on both alkyl chains. We show that 5-HT locates at the hydrophobic-hydrophilic interface, below the glycerol group. This interfacial location is stabilized by hydrogen bonds between the 5-HT hydroxyl group and lipid headgroups and allows 5-HT to intercept reactive oxygen species, preventing membrane oxidation. Experimental and molecular dynamics simulations using membrane enriched with oxidized lipids converge to further reveal that 5-HT contributes to the termination of lipid peroxidation by direct interaction with active groups of these lipids and could also contribute to limit the production of new radicals. Taken together, our results identify 5-HT as a potent inhibitor of lipid peroxidation and offer a different perspective on the role of this pleiotropic molecule.

show abstract

Section: Serotonin Interacts With Lipid Bilayers At the Interfacesupporting

confidence: 93%

Antioxidant and Membrane Binding Properties of Serotonin Protect Lipids from Oxidation

Azouzi

Santuz

Morandat

et al. 2017

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…42 From a thermodynamical point of view, the -COO − group is a "structure-maker," while the -NH 3 + group acts as a "structure-breaker." [43][44][45][46][47] These observations, in combination with recent MD simulations where the -COO − group accommodates more HBs with the proximal water molecules than -NH 3 + , 48,49 imply hydrophilic hydration is dominated by the strong hydration capacity of the -COO − group, with a relatively small contribution from the -NH 3 + group. Based on the RDF of glycine aqueous solution, Campro 49 calculated the to- tal number of HBs between glycine and water, 5.7, which is larger than our result n hyd (gly) = 1.9; suggesting large fraction of the water molecules (i.e., 5.7 − 1.9 = 3.8 molecules) forms relatively weak HBs with the glycine solute, and thus, their reorientational dynamics are hard to distinguish from those of bulk water.…”

Section: B Hydration States In Amino Acid Solutionsmentioning

confidence: 54%

Hydration and hydrogen bond network of water around hydrophobic surface investigated by terahertz spectroscopy

Shiraga

Suzuki

Kondo

et al. 2014

The Journal of Chemical Physics

View full text Add to dashboard Cite

Water conformation around hydrophobic side chains of four amino acids (glycine, L-alanine, L-aminobutyric acid, and L-norvaline) was investigated via changes in complex dielectric constant in the terahertz (THz) region. Each of these amino acids has the same hydrophilic backbone, with successive additions of hydrophobic straight methylene groups (-CH2-) to the side chain. Changes in the degree of hydration (number of dynamically retarded water molecules relative to bulk water) and the structural conformation of the water hydrogen bond (HB) network related to the number of methylene groups were quantitatively measured. Since dielectric responses in the THz region represent water relaxations and water HB vibrations at a sub-picosecond and picosecond timescale, these measurements characterized the water relaxations and HB vibrations perturbed by the methylene apolar groups. We found each successive straight -CH2- group on the side chain restrained approximately two hydrophobic hydration water molecules. Additionally, the number of non-hydrogen-bonded (NHB) water molecules increased slightly around these hydrophobic side chains. The latter result seems to contradict the iceberg model proposed by Frank and Evans, where water molecules are said to be more ordered around apolar surfaces. Furthermore, we compared the water-hydrophilic interactions of the hydrophilic amino acid backbone with those with the water-hydrophobic interactions around the side chains. As the hydrophobicity of the side chain increased, the ordering of the surrounding water HB network was altered from that surrounding the hydrophilic amino acid backbone, thereby diminishing the fraction of NHB water and ordering the surrounding tetrahedral water HB network.

show abstract

“…14 Recent molecular dynamics studies have focused on a wide variety of molecules passively diffusing through membranes, such as water, [15][16][17] small molecules, [18][19][20][21][22][23] model drug compounds, 6,22,24,25 analgesics, [26][27][28] drug delivery systems, 29,30 dyes, 31,32 other lipids, 33,34 nanoparticles, [35][36][37] toxins, 38 small peptides, 39,40 and even transmembrane proteins. 41,42 However, only a handful of MD studies have examined amino acid-related systems and are confined to tryptophan, [43][44][45] arginine, 46,47 lysine, 47 and amino acid analogues. 48 In terms of potential of mean force (PMF), findings have consistently shown that small nonpolar molecules tend to be preferentially bound in the membrane center, while polar molecules tend to interact favorably with the lipid headgroups and experience a free energy barrier in the center.…”

Section: Introductionmentioning

confidence: 99%

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Lee

Kuczera

Middaugh

et al. 2016

The Journal of Chemical Physics

View full text Add to dashboard Cite

The time-resolved parallel artificial membrane permeability assay with fluorescence detection and comprehensive computer simulations are used to study the passive permeation of three aromatic dipeptides—N-acetyl-phenylalanineamide (NAFA), N-acetyltyrosineamide (NAYA), and N-acetyl-tryptophanamide (NATA) through a 1,2-dioleoyl-sn-glycero-3-phospocholine (DOPC) lipid bilayer. Measured permeation times and permeability coefficients show fastest translocation for NAFA, slowest for NAYA, and intermediate for NATA under physiological temperature and pH. Computationally, we perform umbrella sampling simulations to model the structure, dynamics, and interactions of the peptides as a function of z, the distance from lipid bilayer. The calculated profiles of the potential of mean force show two strong effects—preferential binding of each of the three peptides to the lipid interface and large free energy barriers in the membrane center. We use several approaches to calculate the position-dependent translational diffusion coefficients D(z), including one based on numerical solution the Smoluchowski equation. Surprisingly, computed D(z) values change very little with reaction coordinate and are also quite similar for the three peptides studied. In contrast, calculated values of sidechain rotational correlation times τrot(z) show extremely large changes with peptide membrane insertion—values become 100 times larger in the headgroup region and 10 times larger at interface and in membrane center, relative to solution. The peptides’ conformational freedom becomes systematically more restricted as they enter the membrane, sampling α and β and C7eq basins in solution, α and C7eq at the interface, and C7eq only in the center. Residual waters of solvation remain around the peptides even in the membrane center. Overall, our study provides an improved microscopic understanding of passive peptide permeation through membranes, especially on the sensitivity of rotational diffusion to position relative to the bilayer.

show abstract

Similarities and differences of serotonin and its precursors in their interactions with model membranes studied by molecular dynamics simulation

Cited by 18 publications

References 49 publications

Antioxidant and Membrane Binding Properties of Serotonin Protect Lipids from Oxidation

Antioxidant and Membrane Binding Properties of Serotonin Protect Lipids from Oxidation

Hydration and hydrogen bond network of water around hydrophobic surface investigated by terahertz spectroscopy

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Contact Info

Product

Resources

About