Computational drug discovery of potential TAU protein kinase I inhibitors using in silico docking studies

Arumugam Madeswaran,Varadharajan Subhadradevi,Muthuswamy Umamaheswari,Kuppusamy Asokkumar,Thirumalaisamy Sivashanmugam,Puliyath Jagannath

doi:10.3329/bjp.v8i2.13886

Arumugam Madeswaran, Varadharajan Subhadradevi + Show 4 more

Open Access

https://doi.org/10.3329/bjp.v8i2.13886

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Abstract

The objective of the current study is to evaluate the tau protein kinase I inhibitory activity of flavonoids using in silico docking studies. In silico docking studies were carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. Memantine, a known neuro-receptor antagonist is currently used in the treatment of Alzheimer's disease. The results showed that all the selected flavonoids showed binding energy ranging between -7.07 kcal/mol to -4.85 kcal/mol when compared with that of the standard (-5.89 kcal/mol). Inhibition constant (6.62 µM to 280.05 µM) and intermolecular energy (-9.45 kcal/mol to -6.64 kcal/mol) of the ligands also coincide with the binding energy. These molecular docking analyses could lead to the further development of potent tau protein kinase I inhibitors for the treatment of Alzheimers disease. Further investigations on the above compounds and in vivo studies are necessary to develop potential chemical entities for the prevention and treatment of Alzheimer's disease.

Highlights

Rational drug design is the inventive process of finding new medications based on the knowledge of the biological target
Python 2.7-language was downloaded from www.python.com, Cygwin c:\program and Python 2.5 were simultaneously down-loaded from www.cygwin.com, Molecular graphics laboratory (MGL) tools and AutoDock 4.2 was down-loaded from www.scripps.edu, Discovery studio visualizer 2.5.5 was downloaded from www.accelerys.com, Molecular orbital package (MOPAC), ChemSketch was downloaded from www.acdlabs.com
We employed the Lamarckian genetic algorithm (LGA) for ligand conformational searching, which is a hybrid of a genetic algorithm and a local search algorithm

Summary

Introduction

Rational drug design is the inventive process of finding new medications based on the knowledge of the biological target. Drug research aims at the development of a novel therapeutic agent which is done by designing molecules that are complementary in shape and charge to the biomolecular target with which they interact and bind. Drug discovery and develop-ment is an intense, lengthy and an interdisciplinary endeavor. It is a linear, consecutive process that starts with target and lead discovery, followed by lead optimization and pre-clinical in vitro and in vivo studies to determine if such compounds satisfy a number of pre-set criteria for initiating clinical development (Ekins et al, 2005). Its default search function is based on Lamarckian Genetic Algorithm (LGA), a hybrid genetic algorithm with local optimization that uses a parameterized free-energy scoring function to estimate the binding energy (Madeswaran et al, 2012)

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