Paper Info
Title
Exploring Protein-Peptide Binding Specificity through Computational Peptide Screening.
Abstract
The binding of short disordered peptide stretches to globular protein domains is important for a wide range of cellular processes, including signal transduction, protein transport, and immune response. The often promiscuous nature of these interactions and the conformational flexibility of the peptide chain, sometimes even when bound, make the binding specificity of this type of protein interaction a challenge to understand. Here we develop and test a Monte Carlo-based procedure for calculating protein-peptide binding thermodynamics for many sequences in a single run. The method explores both peptide sequence and conformational space simultaneously by simulating a joint probability distribution which, in particular, makes searching through peptide sequence space computationally efficient. To test our method, we apply it to 3 different peptide-binding protein domains and test its ability to capture the experimentally determined specificity profiles. Insight into the molecular underpinnings of the observed specificities is obtained by analyzing the peptide conformational ensembles of a large number of binding-competent sequences. We also explore the possibility of using our method to discover new peptide-binding pockets on protein structures.
Year
DOI
Venue
2013
10.1371/journal.pcbi.1003277
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
protein binding,computational biology,protein conformation,protein domains,free energy,thermodynamics,monte carlo method,protein structure,probability distribution,amino acid sequence,proteins
Protein domain,Biology,Globular protein,Peptide,Conformational ensembles,Binding selectivity,Bioinformatics,Transport protein,Peptide sequence,Protein structure
Journal
Volume
Issue
ISSN
9
10
1553-7358
Citations 
PageRank 
References 
0
0.34
8
Authors
2
Name
Order
Citations
PageRank
Arnab Bhattacherjee100.34
Stefan Wallin2598.01