Role of the Indole Ring on the Localization of Serotonin and Related Molecules in Lipid Bilayers

I. WOOD; M PICKHOLZ

Ouro preto

Simposio; SBQT; 2011

SBQT

Serotonin (5-HT) is a neurotransmitter and hormone implicated in several physiological processes by activating multiple receptors. Abnormalities on the serotoninergic system have been implicated in many psychiatric disorders such as anxiety, depression, psychosis, migraine. Otherwise, 5-HT is synthesized by a two-step reaction from the essential amino acid tryptophan (Trp) through 5- hydroxytryptophan (5-HTP). Besides, drugs such as the triptans were developed as a novel choice for migraine treatment, due to its action like 5-HT receptors agonists. In this work, we use Molecular Dynamic simulations (MDs) to study the interactions of serotonin (5-HT) and its precursors and derived drugs. MDs were performed at constant pressure (1atm) and temperature (310K), in order to 1- palmitoil-2-oleoil-sn-glicero-3-phosphatidyl-choline (POPC) bilayers to be found in the fluid lamellar phase. Five different guest molecules were studied: tryptophan (Trp), 5-hydroxytryptophan (5-HTP), charged and neutral 5-HT and sumatriptan. Each system consists in 2 identical guest molecules, 4200 molecules of water and 150 POPC molecules. Each simulation was run up 50 ns. In order to understand its behavior on lipid bilayers, we study interactions between guest molecules and POPC. From the analysis of the radial distribution function we found that pairs of atoms H indole NH group (guest molecule) and O carbonile group (POPC) shows a well defined peak ~ 1.7 Å, characteristic of hydrogen bond. Taken another pair, the centroid of indole six-membered aromatic ring (guest molecule) and charged head -N(CH3)3+ choline (POPC), we found a well defined peak ~ 4 Å, characteristic of cation-p interaction (see Fig.1)