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. 2013 Aug 28;9(15):771-6.
doi: 10.6026/97320630009771. eCollection 2013.

in-silico study of arylalkylamine-nacetyltransferase enzyme to regulate circadian rhythmicity

Kumar Prashant  1 , Himansu Kumar, Chekkara Venkata Satya Siva Prasad
Affiliations

in-silico study of arylalkylamine-nacetyltransferase enzyme to regulate circadian rhythmicity

Kumar Prashant et al. Bioinformation. .

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.

Keywords: AANAT; Circadian Rhythmicity; Melatonin; N-Acetyl Serotonin; Sleeping Sickness.

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Figures

Figure 1
Figure 1
Ramachandran plot shows 90.9% residues found in allowed region
Figure 2
Figure 2
A) RMSD of backbone atoms shows stable nature of model; B) RMSF graph showing fluctuations in protein with respect to time; C) Graph of potential energy shows the energetically stable conformation.
Figure 3
Figure 3
Showing interaction of ligands (A, B, C, D, E, and F) with receptor protein.
See this image and copyright information in PMC

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