title: In silico study of peptide inhibitors against BACE 1.
abstract: Peptides are increasingly used as inhibitors of various disease specific targets. Several naturally occurring and synthetically developed peptides are undergoing clinical trials. Our work explores the possibility of reusing the non-expressing DNA sequences to predict potential drug-target specific peptides. Recently, we experimentally demonstrated the artificial synthesis of novel proteins from non-coding regions of Escherichia coli genome. In this study, a library of synthetic peptides (Synpeps) was constructed from 2500 intergenic E. coli sequences and screened against Beta-secretase 1 protein, a known drug target for Alzheimer's disease (AD). Secondary and tertiary protein structure predictions followed by protein-protein docking studies were performed to identify the most promising enzyme inhibitors. Interacting residues and favorable binding poses of lead peptide inhibitors were studied. Though initial results are encouraging, experimental validation is required in future to develop efficient target specific inhibitors against AD.
authors.affiliation: Department of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, 695581 Kerala India.
authors.forename: Navya
authors.initials: N
authors.lastname: Raj
authors.affiliation: Department of Bioinformatics, Sathyabhama University, Chennai, 600119 Tamilnadu India.
authors.forename: Agnes
authors.initials: A
authors.lastname: Helen
authors.affiliation: Department of Bioinformatics, Sathyabhama University, Chennai, 600119 Tamilnadu India.
authors.forename: N
authors.initials: N
authors.lastname: Manoj
authors.affiliation: Lifecode Technologies Pvt. Ltd, New Delhi, 110044 India.
authors.forename: G
authors.initials: G
authors.lastname: Harish
authors.affiliation: Department of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, 695581 Kerala India.
authors.forename: Vipin
authors.initials: V
authors.lastname: Thomas
authors.affiliation: Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Greater Noida, 201314 India.
authors.forename: Shailja
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Greater Noida, 201314 India.
authors.forename: Seema
authors.initials: S
authors.lastname: Sehrawat
authors.affiliation: Sporos Therapeutics LLC, Bothell, WA USA.
authors.forename: Shaguna
authors.initials: S
authors.lastname: Seth
authors.affiliation: Department of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, 695581 Kerala India.
authors.forename: Achuthsankar S
authors.initials: AS
authors.lastname: Nair
authors.affiliation: School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067 India.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Grover
authors.affiliation: Department of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, 695581 Kerala India ; School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067 India.
authors.forename: Pawan K
authors.initials: PK
authors.lastname: Dhar
keywords: Alzheimer’s disease; Beta-secretase 1; Junkomics; Not-coding DNA; Synthetic peptides