In-silico study of arylalkylamine-nacetyltransferase enzyme to regulate circadian rhythmicity.

Kumar Prashant,Chekkara Venkata Prasad,Himansu Kumar

doi:10.6026/97320630009771

Kumar Prashant, Chekkara Venkata Prasad + Show 1 more

Open Access

https://doi.org/10.6026/97320630009771

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Abstract

Circadian Rhythmicity is present in the sleeping and breeding patterns of animals, including human beings and also related with brain wave activity, hormone production, cell regeneration and other biological activities. Melatonin is thought to play important roles in regulating circadian rhytmicity of the animals. Arylalkylamine-N-acetyltransferase (AANAT) is an enzyme which is responsible for the melatonin metabolism. In this study AANAT enzyme is targeted for the control of sleeping sickness and other irregular circadian rhythmicity by regulating the melatonin formation. AANAT protein 3D-structure was modeled, followed by loop modeling, refinement through energy minimization processes by molecular dynamics simulation and validation. Analysis of the Ramachandran plot shows 90.9% amino acids falls in the allowed region. The modeled protein was docked with N-Acetyl Serotonin. Combinatorial library was generated by using N-Acetyl Serotonin as a reference molecule and molecules having 80% similarity to N-Acetyl Serotonin was selected from Zinc database. These molecules were virtually screened by MOLEGRO virtual docker and top 5 molecules were selected and docked by using AutoDock. The AutoDock result shows that the ZINC01587152 molecule is having best interactions with the receptor protein. On the basis of this study we can suggest that the ZINC01587152 molecule is the best ligand against AANAT enzyme. It may be further synthesized and tested for sleep related disorders.

Highlights

It is circadian clock in the suprachiasmatic nucleus (SCN), which already reported that the enzyme AANAT would be a good drives rhythmic activity of the pineal gland via neural circuit target for the treatment of irregular circadian rhythmicity and that not passes through central and peripheral structures [5, 6]
All the solvent atom and protein molecules were allowed to relax in Results: Virtual Screening for Ligand Prepration Ligand N-Acetyl Serotonin was used as a reference molecule to generate ligand library from ZINC database
The AANAT is responsible for conversion of serotonin to melatonin and it is observed that it regulates wide variety of sleep disorders. 3D structure AANAT has been modeled and their energy minimization has been performed to bring optimized state later evaluated with Ramachandran Plot

Summary

Introduction

The important regulatory role of of an organism It is visceral and adjusted by environmental AANAT has made it of central interest in research of melatonin factors such as daylight. Studies in the rat balanced formation of melatonin and conversion of melatonin indicates that expression of the AANAT gene is regulated by from serotonin is governed by an enzyme AANAT [1] It is circadian clock in the suprachiasmatic nucleus (SCN), which already reported that the enzyme AANAT would be a good drives rhythmic activity of the pineal gland via neural circuit target for the treatment of irregular circadian rhythmicity and that not passes through central and peripheral structures [5, 6]

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