Computational studies of protein-protein dissociation by statistical potential and coarse-grained simulations

A case study on interactions between colicin E9 endonuclease and immunity proteins

Zhaoqian Su, Yinghao Wu

Research output: Contribution to journalArticle

Abstract

Proteins carry out their diverse functions in cells by forming interactions with each other. The dynamics of these interactions are quantified by the measurement of association and dissociation rate constants. Relative to the efforts made to model the association of biomolecules, little has been studied to understand the principles of protein complex dissociation. Using the interaction between colicin E9 endonucleases and immunity proteins as a test system, here we develop a coarse-grained simulation method to explore the dissociation mechanisms of protein complexes. The interactions between proteins in the complex are described by the knowledge-based potential that was constructed by the statistics from available protein complexes in the structural database. Our study provides the supportive evidences to the dual recognition mechanism for the specificity of binding between E9 DNase and immunity proteins, in which the conserved residues of helix III of Im2 and Im9 proteins act as the anchor for binding, while the sequence variations in helix II make positive or negative contributions to specificity. Beyond that, we further suggest that this binding specificity is rooted in the process of complex dissociation instead of association. While we increased the flexibility of protein complexes, we further found that they are less prone to dissociation, suggesting that conformational fluctuations of protein complexes play important functional roles in regulating their binding and dissociation. Our studies therefore bring new insights to the molecule mechanisms of protein-protein interactions, while the method can serve as a new addition to a suite of existing computational tools for the simulations of protein complexes.

Original languageEnglish (US)
Pages (from-to)2463-2471
Number of pages9
JournalPhysical Chemistry Chemical Physics
Volume21
Issue number5
DOIs
StatePublished - Jan 1 2019

Fingerprint

Colicins
Endonucleases
immunity
dissociation
proteins
Proteins
simulation
interactions
Association reactions
helices
Deoxyribonucleases
Biomolecules
Anchors

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Physical and Theoretical Chemistry

Cite this

@article{96740a289c5c471495c0fe77e3f24ad5,
title = "Computational studies of protein-protein dissociation by statistical potential and coarse-grained simulations: A case study on interactions between colicin E9 endonuclease and immunity proteins",
abstract = "Proteins carry out their diverse functions in cells by forming interactions with each other. The dynamics of these interactions are quantified by the measurement of association and dissociation rate constants. Relative to the efforts made to model the association of biomolecules, little has been studied to understand the principles of protein complex dissociation. Using the interaction between colicin E9 endonucleases and immunity proteins as a test system, here we develop a coarse-grained simulation method to explore the dissociation mechanisms of protein complexes. The interactions between proteins in the complex are described by the knowledge-based potential that was constructed by the statistics from available protein complexes in the structural database. Our study provides the supportive evidences to the dual recognition mechanism for the specificity of binding between E9 DNase and immunity proteins, in which the conserved residues of helix III of Im2 and Im9 proteins act as the anchor for binding, while the sequence variations in helix II make positive or negative contributions to specificity. Beyond that, we further suggest that this binding specificity is rooted in the process of complex dissociation instead of association. While we increased the flexibility of protein complexes, we further found that they are less prone to dissociation, suggesting that conformational fluctuations of protein complexes play important functional roles in regulating their binding and dissociation. Our studies therefore bring new insights to the molecule mechanisms of protein-protein interactions, while the method can serve as a new addition to a suite of existing computational tools for the simulations of protein complexes.",
author = "Zhaoqian Su and Yinghao Wu",
year = "2019",
month = "1",
day = "1",
doi = "10.1039/c8cp05644g",
language = "English (US)",
volume = "21",
pages = "2463--2471",
journal = "Physical Chemistry Chemical Physics",
issn = "1463-9076",
publisher = "Royal Society of Chemistry",
number = "5",

}

TY - JOUR

T1 - Computational studies of protein-protein dissociation by statistical potential and coarse-grained simulations

T2 - A case study on interactions between colicin E9 endonuclease and immunity proteins

AU - Su, Zhaoqian

AU - Wu, Yinghao

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Proteins carry out their diverse functions in cells by forming interactions with each other. The dynamics of these interactions are quantified by the measurement of association and dissociation rate constants. Relative to the efforts made to model the association of biomolecules, little has been studied to understand the principles of protein complex dissociation. Using the interaction between colicin E9 endonucleases and immunity proteins as a test system, here we develop a coarse-grained simulation method to explore the dissociation mechanisms of protein complexes. The interactions between proteins in the complex are described by the knowledge-based potential that was constructed by the statistics from available protein complexes in the structural database. Our study provides the supportive evidences to the dual recognition mechanism for the specificity of binding between E9 DNase and immunity proteins, in which the conserved residues of helix III of Im2 and Im9 proteins act as the anchor for binding, while the sequence variations in helix II make positive or negative contributions to specificity. Beyond that, we further suggest that this binding specificity is rooted in the process of complex dissociation instead of association. While we increased the flexibility of protein complexes, we further found that they are less prone to dissociation, suggesting that conformational fluctuations of protein complexes play important functional roles in regulating their binding and dissociation. Our studies therefore bring new insights to the molecule mechanisms of protein-protein interactions, while the method can serve as a new addition to a suite of existing computational tools for the simulations of protein complexes.

AB - Proteins carry out their diverse functions in cells by forming interactions with each other. The dynamics of these interactions are quantified by the measurement of association and dissociation rate constants. Relative to the efforts made to model the association of biomolecules, little has been studied to understand the principles of protein complex dissociation. Using the interaction between colicin E9 endonucleases and immunity proteins as a test system, here we develop a coarse-grained simulation method to explore the dissociation mechanisms of protein complexes. The interactions between proteins in the complex are described by the knowledge-based potential that was constructed by the statistics from available protein complexes in the structural database. Our study provides the supportive evidences to the dual recognition mechanism for the specificity of binding between E9 DNase and immunity proteins, in which the conserved residues of helix III of Im2 and Im9 proteins act as the anchor for binding, while the sequence variations in helix II make positive or negative contributions to specificity. Beyond that, we further suggest that this binding specificity is rooted in the process of complex dissociation instead of association. While we increased the flexibility of protein complexes, we further found that they are less prone to dissociation, suggesting that conformational fluctuations of protein complexes play important functional roles in regulating their binding and dissociation. Our studies therefore bring new insights to the molecule mechanisms of protein-protein interactions, while the method can serve as a new addition to a suite of existing computational tools for the simulations of protein complexes.

UR - http://www.scopus.com/inward/record.url?scp=85060797363&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060797363&partnerID=8YFLogxK

U2 - 10.1039/c8cp05644g

DO - 10.1039/c8cp05644g

M3 - Article

VL - 21

SP - 2463

EP - 2471

JO - Physical Chemistry Chemical Physics

JF - Physical Chemistry Chemical Physics

SN - 1463-9076

IS - 5

ER -