Analysis and subsequent molecular docking of selected phytochemicals with SLC6A3 and SLC6A4 as potential therapeutic agents for Obsessive-Compulsive Disorder (OCD)

Abstract

Obsessive-Compulsive Disorder (OCD) is one of the most problematic disorders of the brain. It lies in the category of moodomics disorders and can be identified by the presence of recurring intrusive thoughts (\"compulsions\") and urges to do certain things repeatedly (\"obsessions\"), with a definite lack of control on these tendencies and their intensity affecting the patients daily life. It is known to be associated with not only anxiety disorder but also depression, with its cause being unknown, although possessing genetic components. Several separate methods are being attempted to develop an effective therapy for OCD but this field of research requires more focus. In the present course of research, there is an attempt to signify the molecular analysis approach by testing potential drugs computationally with previously identified targets, i. e. dopamine active transporter (DAT or SLC6A3) and sodium-dependent serotonin transporter (SERT or 5-HTT or SLC6A4) - two proteins which have been observed playing a major role in the manifestation of OCD symptoms. Their 3D structure prediction has already been done in the previous course of study. In continuation to the previous study, there is an attempt to screen out the potentially useful phytochemicals against this moodomics disorder. Several potentially useful phytochemicals are known to associate with SLC6A3 and SLC6A4, which have been identified through the text mining of various publications. First of all, these phytochemicals are analysed through the use of Molinspiration software followed by selection of the ones suitable as drug candidates using Lipinskis Rule of five and finally, best docking configurations identified using AutoDock 4 in order to obtain potential therapeutics for OCD patients. Nuciferine, Epicatechin (EC), Retinal, Aphidicolin and Salvinorin A are showing good docking scores but among all these phytochemicals, Nuciferin, an extract of Indian Lotus plant, appears to be the one most suitable compound on the basis of binding energy calculations. Hence, we can say this could be a good revealing therapeutic agent for this disorder.