Kirkwood-Buff Approach Rescues Overcollapse of a Disordered Protein in Canonical Protein Force Fields

Autoren

Davide Mercadante
Sigrid Milles
Gustavo Fuertes
Dmitri I Svergun
Edward A Lemke
Frauke Gräter

DOI

10.1021/acs.jpcb.5b03440

eISSN

1520-5207

ISSN

1520-6106

Ausgabe der Veröffentlichung

25

Zeitschrift

The Journal of Physical Chemistry B

Sprache

en

Online publication date

2015

Paginierung

7975 - 7984

Datum der Veröffentlichung

2015

Status

Published

Herausgeber

American Chemical Society (ACS)

Herausgeber URL

http://dx.doi.org/10.1021/acs.jpcb.5b03440

Datum der Datenerfassung

2024

Titel

Kirkwood–Buff Approach Rescues Overcollapse of a Disordered Protein in Canonical Protein Force Fields

Ausgabe der Zeitschrift

119

Datenquelle: Crossref

Abstract

Understanding the function of intrinsically disordered proteins is intimately related to our capacity to correctly sample their conformational dynamics. So far, a gap between experimentally and computationally derived ensembles exists, as simulations show overcompacted conformers. Increasing evidence suggests that the solvent plays a crucial role in shaping the ensembles of intrinsically disordered proteins and has led to several attempts to modify water parameters and thereby favor protein-water over protein-protein interactions. This study tackles the problem from a different perspective, which is the use of the Kirkwood-Buff theory of solutions to reproduce the correct conformational ensemble of intrinsically disordered proteins (IDPs). A protein force field recently developed on such a basis was found to be highly effective in reproducing ensembles for a fragment from the FG-rich nucleoporin 153, with dimensions matching experimental values obtained from small-angle X-ray scattering and single molecule FRET experiments. Kirkwood-Buff theory presents a complementary and fundamentally different approach to the recently developed four-site TIP4P-D water model, both of which can rescue the overcollapse observed in IDPs with canonical protein force fields. As such, our study provides a new route for tackling the deficiencies of current protein force fields in describing protein solvation.

Addresses

†HITS-Heidelberg Institut for Theoretical Studies, Schloß-Wolfsbrunnenweg 35, 69118, Heidelberg, Germany.

Autoren

Davide Mercadante
Sigrid Milles
Gustavo Fuertes
Dmitri I Svergun
Edward A Lemke
Frauke Gräter

DOI

10.1021/acs.jpcb.5b03440

eISSN

1520-5207

Externe Identifier

PubMed Identifier: 26030189

Funding acknowledgements

Boehringer Ingelheim Fonds:
Deutsche Forschungsgemeinschaft:
European Commission Directorate-General for Research and Innovation:
Klaus Tschira Stiftung:

Open access

false

ISSN

1520-6106

Ausgabe der Veröffentlichung

25

Zeitschrift

The journal of physical chemistry. B

Schlüsselwörter

Humans
Escherichia coli
Water
Nuclear Pore Complex Proteins
Solutions
X-Ray Diffraction
Fluorescence Resonance Energy Transfer
Monte Carlo Method
Protein Conformation
Models, Chemical
Scattering, Small Angle
Molecular Dynamics Simulation
Intrinsically Disordered Proteins

Sprache

eng

Medium

Print-Electronic

Online publication date

2015

Paginierung

7975 - 7984

Datum der Veröffentlichung

2015

Status

Published

Datum der Datenerfassung

2015

Titel

Kirkwood-Buff Approach Rescues Overcollapse of a Disordered Protein in Canonical Protein Force Fields.

Sub types

Comparative Study
Research Support, Non-U.S. Gov't
Journal Article

Ausgabe der Zeitschrift

119

Datenquelle: Europe PubMed Central

Abstract

Understanding the function of intrinsically disordered proteins is intimately related to our capacity to correctly sample their conformational dynamics. So far, a gap between experimentally and computationally derived ensembles exists, as simulations show overcompacted conformers. Increasing evidence suggests that the solvent plays a crucial role in shaping the ensembles of intrinsically disordered proteins and has led to several attempts to modify water parameters and thereby favor protein-water over protein-protein interactions. This study tackles the problem from a different perspective, which is the use of the Kirkwood-Buff theory of solutions to reproduce the correct conformational ensemble of intrinsically disordered proteins (IDPs). A protein force field recently developed on such a basis was found to be highly effective in reproducing ensembles for a fragment from the FG-rich nucleoporin 153, with dimensions matching experimental values obtained from small-angle X-ray scattering and single molecule FRET experiments. Kirkwood-Buff theory presents a complementary and fundamentally different approach to the recently developed four-site TIP4P-D water model, both of which can rescue the overcollapse observed in IDPs with canonical protein force fields. As such, our study provides a new route for tackling the deficiencies of current protein force fields in describing protein solvation.

Autoren

Davide Mercadante
Sigrid Milles
Gustavo Fuertes
Dmitri I Svergun
Edward A Lemke
Frauke Gräter

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/26030189

DOI

10.1021/acs.jpcb.5b03440

eISSN

1520-5207

Ausgabe der Veröffentlichung

25

Zeitschrift

J Phys Chem B

Schlüsselwörter

Escherichia coli
Fluorescence Resonance Energy Transfer
Humans
Intrinsically Disordered Proteins
Models, Chemical
Molecular Dynamics Simulation
Monte Carlo Method
Nuclear Pore Complex Proteins
Protein Conformation
Scattering, Small Angle
Solutions
Water
X-Ray Diffraction

Sprache

eng

Country

United States

Paginierung

7975 - 7984

Datum der Veröffentlichung

2015

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2016

Titel

Kirkwood-Buff Approach Rescues Overcollapse of a Disordered Protein in Canonical Protein Force Fields.

Sub types

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

119

Datenquelle: PubMed

Kirkwood-Buff Approach Rescues Overcollapse of a Disordered Protein in Canonical Protein Force Fields

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