Journal of Computational Methods in Molecular Design, 2014, 4 (1):14-24 Scholars Research Library (http://scholarsresearchlibrary.com/archive.html) ISSN : 2231- 3176 CODEN (USA): JCMMDA 14 Available online at www.scholarsresearchlibrary.com Targeting BACE 1(Beta secretase) through Polyphenolic compounds -A computational insilico approach with emphasis on binding site analysis *Karthik Dhananjayan 1 , Sumathy Arunachalam 2 , Baskar Anand Raj 3 1 Department of Pharmacology, Molecular Pharmacology and Drug screening division, Grace College of Pharmacy, Athalur, Kodunthirapully post, Palakkad, Kerala, INDIA. 2 Department of Pharmaceutical Chemistry, Grace College of Pharmacy, Athalur, Kodunthirapully post, Palakkad, Kerala State, INDIA. 3 Department of Pharmacognosy, Padmavathy college of Pharmacy, Dharmapuri, Tamilnadu, INDIA _____________________________________________________________________________________________ ABSTRACT Polyphenolic compounds posses vast number of biological activities and they are the inclusions of phyto- constituents of plant kingdom. Synthetic drugs used in the treatment of neurodegenerative disorders like Alzheimer’s disease is of only symptomatic and for not permanent cure over the progression of the disease. Beta secretase- 1(BACE1) is aspartic protease makes improper cleavage of amyloid precursor protein (APP) found on the membrane of the neuronal cells and produces the accumulation of beta amyloid proteins of insoluble fractions. Polyphenolic compounds like catechin3gallate, hesperidin, hesperitin etc., were found to possess lowest binding energy with best conformation, when comparing with the standard reference ligands. In this insilico docking studies, it revealed that targeting BACE1 inhibition, through Polyphenolic compounds can create number of lead molecules for better therapeutic concern in future. Key words: Polyphenolic compounds, Beta secretase, Alzheimer’s disease, MVD 6.O _____________________________________________________________________________________________ INTRODUCTION Computational methodologies and their tools made drug discovery process less time consuming and decreased the usage of animals in prior to preclinical studies. In silico studies were employed for the simulation of physiological systems including physiological macromolecules like receptors, enzymes were designed using modeling softwares and analysed for their simulating activities. In this advanced drug discovery process the simulated proteins can be targeted, if any underlying implications are because of all those enzymes. Naturally occurring phyto-compounds, such as polyphenolic antioxidants found in fruits, vegetables, herbs and nuts, may potentially hinder neurodegeneration, and improve memory and cognitive function [1]. Neurodegenerative disorders like Alzheimer’s disease (AD) is thought to be caused by the progressive brain accumulation of β-amyloid (Ab) peptides into fibrillar aggregates and insoluble plaques resulting severe memory loss and neuronal cell death [2]. AD develops gradually and induces memory loss, unusual behavior, personality changes, and a general decline in thinking abilities and it affects people above the age of 60. A non peptide, optimum molecular weight, potent BACE1 inhibitors development is of major importance [3].In such a way the non-peptidic inhibitors are of increasing importance in order to cross the blood brain barrier and after crossing BBB it to be escaped from