Mapping the Protein Fold Universe Using the CamTube Force Field in Molecular Dynamics Simulations

G.M. Ku, A. Kannan, M.J.J. Dijkstra, S. Abeln, C. Camilloni, M. Vendruscolo

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

It has been recently shown that the coarse-graining of the structures of polypeptide chains as self-avoiding tubes can provide an effective representation of the conformational space of proteins. In order to fully exploit the opportunities offered by such a ‘tube model’ approach, we present here a strategy to combine it with molecular dynamics simulations. This strategy is based on the incorporation of the ‘CamTube’ force field into the Gromacs molecular dynamics package. By considering the case of a 60-residue polyvaline chain, we show that CamTube molecular dynamics simulations can comprehensively explore the conformational space of proteins. We obtain this result by a 20 μs metadynamics simulation of the polyvaline chain that recapitulates the currently known protein fold universe. We further show that, if residue-specific interaction potentials are added to the CamTube force field, it is possible to fold a protein into a topology close to that of its native state. These results illustrate how the CamTube force field can be used to explore efficiently the universe of protein folds with good accuracy and very limited computational cost.
Original languageEnglish
JournalPLoS Computational Biology
Volume11
Issue number10
DOIs
Publication statusPublished - 2015

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molecular dynamics
Force Field
Molecular Dynamics Simulation
Molecular dynamics
Fold
fold
Proteins
Protein
protein
Computer simulation
simulation
proteins
Tube
Coarse-graining
Polypeptides
Molecular Dynamics
topology
Computational Cost
polypeptides
Topology

Cite this

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title = "Mapping the Protein Fold Universe Using the CamTube Force Field in Molecular Dynamics Simulations",
abstract = "It has been recently shown that the coarse-graining of the structures of polypeptide chains as self-avoiding tubes can provide an effective representation of the conformational space of proteins. In order to fully exploit the opportunities offered by such a ‘tube model’ approach, we present here a strategy to combine it with molecular dynamics simulations. This strategy is based on the incorporation of the ‘CamTube’ force field into the Gromacs molecular dynamics package. By considering the case of a 60-residue polyvaline chain, we show that CamTube molecular dynamics simulations can comprehensively explore the conformational space of proteins. We obtain this result by a 20 μs metadynamics simulation of the polyvaline chain that recapitulates the currently known protein fold universe. We further show that, if residue-specific interaction potentials are added to the CamTube force field, it is possible to fold a protein into a topology close to that of its native state. These results illustrate how the CamTube force field can be used to explore efficiently the universe of protein folds with good accuracy and very limited computational cost.",
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Mapping the Protein Fold Universe Using the CamTube Force Field in Molecular Dynamics Simulations. / Ku, G.M.; Kannan, A.; Dijkstra, M.J.J.; Abeln, S.; Camilloni, C.; Vendruscolo, M.

In: PLoS Computational Biology, Vol. 11, No. 10, 2015.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Mapping the Protein Fold Universe Using the CamTube Force Field in Molecular Dynamics Simulations

AU - Ku, G.M.

AU - Kannan, A.

AU - Dijkstra, M.J.J.

AU - Abeln, S.

AU - Camilloni, C.

AU - Vendruscolo, M.

PY - 2015

Y1 - 2015

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AB - It has been recently shown that the coarse-graining of the structures of polypeptide chains as self-avoiding tubes can provide an effective representation of the conformational space of proteins. In order to fully exploit the opportunities offered by such a ‘tube model’ approach, we present here a strategy to combine it with molecular dynamics simulations. This strategy is based on the incorporation of the ‘CamTube’ force field into the Gromacs molecular dynamics package. By considering the case of a 60-residue polyvaline chain, we show that CamTube molecular dynamics simulations can comprehensively explore the conformational space of proteins. We obtain this result by a 20 μs metadynamics simulation of the polyvaline chain that recapitulates the currently known protein fold universe. We further show that, if residue-specific interaction potentials are added to the CamTube force field, it is possible to fold a protein into a topology close to that of its native state. These results illustrate how the CamTube force field can be used to explore efficiently the universe of protein folds with good accuracy and very limited computational cost.

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