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 drugtarget 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 proteinprotein 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.

Repurposing the dark genome. II - Reverse Proteins

“…The present reverse protein study derives its genesis from the dark genome paper that provided proof of the concept of making functional genes and proteins from intergenic sequences (Dhar et al, 2009). Subsequently, dark genome sequences were artificially expressed in E.coli, D.melanogaster and S.cerevisiae leading to antimalarial, antimicrobial and anti-cancer molecules (Joshi et al, 2013, Raj et al, 2015, Deepthi et al, 2017. Recently, tRNA sequences were used to produce tREPs (tRNA encoded peptides) showing a strong anti-leishmania properties (Chakrabarti et al, 2022).…”

“…melanogaster and S . cerevisiae leading to antimalarial, antimicrobial and anti-cancer molecules (Joshi et al, 2013, Raj et al, 2015, Deepthi et al, 2017). Recently, tRNA sequences were used to produce tREPs (tRNA encoded peptides) showing a strong anti-leishmania properties (Chakrabarti et al, 2022).…”

Translational synthetic biology

“…Likewise in a rat model of Parkinson Disease, a synthetic zinc finger targeting the glial derived neurotrophic factor (GDNF) was found to be neuroprotective (Laganiere et al 2010). A recent study has demonstrated that several peptide inhibitors against Beta-secretase 1 (Raj et al 2015) is a prime therapeutic target for reducing cerebral amyloid beta concentrations in Alzhemier's patients (Yan and Vassar 2014).…”