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Exploring Protein-Peptide Binding Specificity through Computational Peptide Screening.

Bhattacherjee, Arnab LU and Wallin, Stefan LU (2013) In PLoS Computational Biology 9(10).
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Computational Biology
volume
9
issue
10
publisher
Public Library of Science
external identifiers
  • pmid:24204228
  • wos:000330355300037
  • scopus:84887282233
ISSN
1553-7358
DOI
10.1371/journal.pcbi.1003277
language
English
LU publication?
yes
id
4ade5aa8-b548-4374-8384-ddc3c506bc0c (old id 4179688)
date added to LUP
2013-12-05 09:44:37
date last changed
2019-02-20 02:25:52
@article{4ade5aa8-b548-4374-8384-ddc3c506bc0c,
  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.},
  articleno    = {e1003277},
  author       = {Bhattacherjee, Arnab and Wallin, Stefan},
  issn         = {1553-7358},
  language     = {eng},
  number       = {10},
  publisher    = {Public Library of Science},
  series       = {PLoS Computational Biology},
  title        = {Exploring Protein-Peptide Binding Specificity through Computational Peptide Screening.},
  url          = {http://dx.doi.org/10.1371/journal.pcbi.1003277},
  volume       = {9},
  year         = {2013},
}