Implications from a network-based topological analysis of ubiquitin unfolding simulations

Arun Krishnan, Alessandro Giuliani, Joseph P. Zbilut, Masaru Tomita

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: The architectural organization of protein structures has been the focus of intense research since it can hopefully lead to an understanding of how proteins fold. In earlier works we had attempted to identify the inherent structural organization in proteins through a study of protein topology. We obtained a modular partitioning of protein structures with the modules correlating well with experimental evidence of early folding units or "foldons". Residues that connect different modules were shown to be those that were protected during the transition phase of folding. Methodology/Principal Findings: In this work, we follow the topological path of ubiquitin through molecular dynamics unfolding simulations. We observed that the use of recurrence quantification analysis (RQA) could lead to the identification of the transition state during unfolding. Additionally, our earlier contention that the modules uncovered through our graph partitioning approach correlated well with early folding units was vindicated through our simulations. Moreover, residues identified from native structure as connector hubs and which had been shown to be those that were protected during the transition phase of folding were indeed more stable (less flexible) well beyond the transition state. Further analysis of the topological pathway suggests that the all pairs shortest path in a protein is minimized during folding. Conclusions: We observed that treating a protein native structure as a network by having amino acid residues as nodes and the non-covalent interactions among them as links allows for the rationalization of many aspects of the folding process. The possibility to derive this information directly from 3D structure opens the way to the prediction of important residues in proteins, while the confirmation of the minimization of APSP for folding allows for the establishment of a potentially useful proxy for kinetic optimality in the validation of sequence-structure predictions.

Original languageEnglish
Article numbere2149
JournalPLoS One
Volume3
Issue number5
DOIs
Publication statusPublished - 2008 May 14

Fingerprint

ubiquitin
Ubiquitin
Proteins
proteins
protein structure
phase transition
Phase Transition
prediction
molecular dynamics
topology
Proxy
Molecular Dynamics Simulation
Molecular dynamics
kinetics
amino acids
Topology
Amino Acids
Recurrence
Kinetics
Computer simulation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Implications from a network-based topological analysis of ubiquitin unfolding simulations. / Krishnan, Arun; Giuliani, Alessandro; Zbilut, Joseph P.; Tomita, Masaru.

In: PLoS One, Vol. 3, No. 5, e2149, 14.05.2008.

Research output: Contribution to journalArticle

Krishnan, Arun ; Giuliani, Alessandro ; Zbilut, Joseph P. ; Tomita, Masaru. / Implications from a network-based topological analysis of ubiquitin unfolding simulations. In: PLoS One. 2008 ; Vol. 3, No. 5.
@article{dffa284341994484bfe337f0dd9e0ef0,
title = "Implications from a network-based topological analysis of ubiquitin unfolding simulations",
abstract = "Background: The architectural organization of protein structures has been the focus of intense research since it can hopefully lead to an understanding of how proteins fold. In earlier works we had attempted to identify the inherent structural organization in proteins through a study of protein topology. We obtained a modular partitioning of protein structures with the modules correlating well with experimental evidence of early folding units or {"}foldons{"}. Residues that connect different modules were shown to be those that were protected during the transition phase of folding. Methodology/Principal Findings: In this work, we follow the topological path of ubiquitin through molecular dynamics unfolding simulations. We observed that the use of recurrence quantification analysis (RQA) could lead to the identification of the transition state during unfolding. Additionally, our earlier contention that the modules uncovered through our graph partitioning approach correlated well with early folding units was vindicated through our simulations. Moreover, residues identified from native structure as connector hubs and which had been shown to be those that were protected during the transition phase of folding were indeed more stable (less flexible) well beyond the transition state. Further analysis of the topological pathway suggests that the all pairs shortest path in a protein is minimized during folding. Conclusions: We observed that treating a protein native structure as a network by having amino acid residues as nodes and the non-covalent interactions among them as links allows for the rationalization of many aspects of the folding process. The possibility to derive this information directly from 3D structure opens the way to the prediction of important residues in proteins, while the confirmation of the minimization of APSP for folding allows for the establishment of a potentially useful proxy for kinetic optimality in the validation of sequence-structure predictions.",
author = "Arun Krishnan and Alessandro Giuliani and Zbilut, {Joseph P.} and Masaru Tomita",
year = "2008",
month = "5",
day = "14",
doi = "10.1371/journal.pone.0002149",
language = "English",
volume = "3",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

TY - JOUR

T1 - Implications from a network-based topological analysis of ubiquitin unfolding simulations

AU - Krishnan, Arun

AU - Giuliani, Alessandro

AU - Zbilut, Joseph P.

AU - Tomita, Masaru

PY - 2008/5/14

Y1 - 2008/5/14

N2 - Background: The architectural organization of protein structures has been the focus of intense research since it can hopefully lead to an understanding of how proteins fold. In earlier works we had attempted to identify the inherent structural organization in proteins through a study of protein topology. We obtained a modular partitioning of protein structures with the modules correlating well with experimental evidence of early folding units or "foldons". Residues that connect different modules were shown to be those that were protected during the transition phase of folding. Methodology/Principal Findings: In this work, we follow the topological path of ubiquitin through molecular dynamics unfolding simulations. We observed that the use of recurrence quantification analysis (RQA) could lead to the identification of the transition state during unfolding. Additionally, our earlier contention that the modules uncovered through our graph partitioning approach correlated well with early folding units was vindicated through our simulations. Moreover, residues identified from native structure as connector hubs and which had been shown to be those that were protected during the transition phase of folding were indeed more stable (less flexible) well beyond the transition state. Further analysis of the topological pathway suggests that the all pairs shortest path in a protein is minimized during folding. Conclusions: We observed that treating a protein native structure as a network by having amino acid residues as nodes and the non-covalent interactions among them as links allows for the rationalization of many aspects of the folding process. The possibility to derive this information directly from 3D structure opens the way to the prediction of important residues in proteins, while the confirmation of the minimization of APSP for folding allows for the establishment of a potentially useful proxy for kinetic optimality in the validation of sequence-structure predictions.

AB - Background: The architectural organization of protein structures has been the focus of intense research since it can hopefully lead to an understanding of how proteins fold. In earlier works we had attempted to identify the inherent structural organization in proteins through a study of protein topology. We obtained a modular partitioning of protein structures with the modules correlating well with experimental evidence of early folding units or "foldons". Residues that connect different modules were shown to be those that were protected during the transition phase of folding. Methodology/Principal Findings: In this work, we follow the topological path of ubiquitin through molecular dynamics unfolding simulations. We observed that the use of recurrence quantification analysis (RQA) could lead to the identification of the transition state during unfolding. Additionally, our earlier contention that the modules uncovered through our graph partitioning approach correlated well with early folding units was vindicated through our simulations. Moreover, residues identified from native structure as connector hubs and which had been shown to be those that were protected during the transition phase of folding were indeed more stable (less flexible) well beyond the transition state. Further analysis of the topological pathway suggests that the all pairs shortest path in a protein is minimized during folding. Conclusions: We observed that treating a protein native structure as a network by having amino acid residues as nodes and the non-covalent interactions among them as links allows for the rationalization of many aspects of the folding process. The possibility to derive this information directly from 3D structure opens the way to the prediction of important residues in proteins, while the confirmation of the minimization of APSP for folding allows for the establishment of a potentially useful proxy for kinetic optimality in the validation of sequence-structure predictions.

UR - http://www.scopus.com/inward/record.url?scp=47749130443&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47749130443&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0002149

DO - 10.1371/journal.pone.0002149

M3 - Article

C2 - 18478068

AN - SCOPUS:47749130443

VL - 3

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 5

M1 - e2149

ER -