Binding Free Energy Landscape of Domain-Peptide Interactions
(2011) In PLoS Computational Biology 7(8).- Abstract
- Peptide recognition domains (PRDs) are ubiquitous protein domains which mediate large numbers of protein interactions in the cell. How these PRDs are able to recognize peptide sequences in a rapid and specific manner is incompletely understood. We explore the peptide binding process of PDZ domains, a large PRD family, from an equilibrium perspective using an all-atom Monte Carlo (MC) approach. Our focus is two different PDZ domains representing two major PDZ classes, I and II. For both domains, a binding free energy surface with a strong bias toward the native bound state is found. Moreover, both domains exhibit a binding process in which the peptides are mostly either bound at the PDZ binding pocket or else interact little with the domain... (More)
- Peptide recognition domains (PRDs) are ubiquitous protein domains which mediate large numbers of protein interactions in the cell. How these PRDs are able to recognize peptide sequences in a rapid and specific manner is incompletely understood. We explore the peptide binding process of PDZ domains, a large PRD family, from an equilibrium perspective using an all-atom Monte Carlo (MC) approach. Our focus is two different PDZ domains representing two major PDZ classes, I and II. For both domains, a binding free energy surface with a strong bias toward the native bound state is found. Moreover, both domains exhibit a binding process in which the peptides are mostly either bound at the PDZ binding pocket or else interact little with the domain surface. Consistent with this, various binding observables show a temperature dependence well described by a simple two-state model. We also find important differences in the details between the two domains. While both domains exhibit well-defined binding free energy barriers, the class I barrier is significantly weaker than the one for class II. To probe this issue further, we apply our method to a PDZ domain with dual specificity for class I and II peptides, and find an analogous difference in their binding free energy barriers. Lastly, we perform a large number of fixed-temperature MC kinetics trajectories under binding conditions. These trajectories reveal significantly slower binding dynamics for the class II domain relative to class I. Our combined results are consistent with a binding mechanism in which the peptide C terminal residue binds in an initial, rate-limiting step. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2159131
- author
- Staneva, Iskra LU and Wallin, Stefan LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS Computational Biology
- volume
- 7
- issue
- 8
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000294299700013
- scopus:80052312953
- pmid:21876662
- ISSN
- 1553-7358
- DOI
- 10.1371/journal.pcbi.1002131
- language
- English
- LU publication?
- yes
- id
- 2d1d1258-5f27-4717-b6c1-76b5806464f6 (old id 2159131)
- date added to LUP
- 2016-04-01 10:11:11
- date last changed
- 2024-03-09 15:14:12
@article{2d1d1258-5f27-4717-b6c1-76b5806464f6,
abstract = {{Peptide recognition domains (PRDs) are ubiquitous protein domains which mediate large numbers of protein interactions in the cell. How these PRDs are able to recognize peptide sequences in a rapid and specific manner is incompletely understood. We explore the peptide binding process of PDZ domains, a large PRD family, from an equilibrium perspective using an all-atom Monte Carlo (MC) approach. Our focus is two different PDZ domains representing two major PDZ classes, I and II. For both domains, a binding free energy surface with a strong bias toward the native bound state is found. Moreover, both domains exhibit a binding process in which the peptides are mostly either bound at the PDZ binding pocket or else interact little with the domain surface. Consistent with this, various binding observables show a temperature dependence well described by a simple two-state model. We also find important differences in the details between the two domains. While both domains exhibit well-defined binding free energy barriers, the class I barrier is significantly weaker than the one for class II. To probe this issue further, we apply our method to a PDZ domain with dual specificity for class I and II peptides, and find an analogous difference in their binding free energy barriers. Lastly, we perform a large number of fixed-temperature MC kinetics trajectories under binding conditions. These trajectories reveal significantly slower binding dynamics for the class II domain relative to class I. Our combined results are consistent with a binding mechanism in which the peptide C terminal residue binds in an initial, rate-limiting step.}},
author = {{Staneva, Iskra and Wallin, Stefan}},
issn = {{1553-7358}},
language = {{eng}},
number = {{8}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS Computational Biology}},
title = {{Binding Free Energy Landscape of Domain-Peptide Interactions}},
url = {{http://dx.doi.org/10.1371/journal.pcbi.1002131}},
doi = {{10.1371/journal.pcbi.1002131}},
volume = {{7}},
year = {{2011}},
}