Title: Computational analysis for functional and evolutionary aspects of BACE-1 and associated Alzheimer's related proteins

Authors: Priya P. Panigrahi; Tiratha Raj Singh

Addresses: Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, P.O. Waknaghat, Teh. Kandaghat, Dt. Solan-173234 (HP), India. ' Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, P.O. Waknaghat, Teh. Kandaghat, Dt. Solan-173234 (HP), India

Abstract: Alzheimer's disease (AD) is an irremediable, heterogeneous, progressive brain disease that slowly destroys memory and judgment skills. We studied the protein-protein interactions of BACE-1 (ß-secretase-1) and select some important proteins for further annotation. MSA for homologs to BACE-1 has been generated to identify functional motifs. To elucidate the structural, functional and evolutionary conservation of these motifs, we performed analysis through ConSeq and ConSurf servers. We found some specific information and clues of interest based on combinational phylogenetic and pattern finding analysis, which can be further targeted for the design of new inhibitors and will help in the inhibition of ß-secretase. Motifs include the active site of the molecule and are found functionally and evolutionarily conserved. This study will also help in elucidating regulation mechanism of proteins found from interaction studies and will help in the design of inhibitors for their activity leads to Alzheimer directly or indirectly. Design of such inhibitors will be a promising approach for the prevention and cure of AD.

Keywords: Alzheimer's disease; system biology; protein-protein interactions; PPI; computational analysis; BACE-1; amyloid precursor protein; APP; functional motifs; inhibitors; inhibitor design; bioinfomatics.

DOI: 10.1504/IJCISTUDIES.2012.050355

International Journal of Computational Intelligence Studies, 2012 Vol.1 No.4, pp.322 - 332

Received: 12 Jan 2012
Accepted: 09 Feb 2012
Published online: 28 Aug 2014 *

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