Mapping the Protein Fold Universe Using the CamTube Force Field in Molecular Dynamics Simulations.
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.
Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
Predrag
P
Kukic
Department of Chemistry, University of Cambridge, Cambridge, United Kingdom; Departments of Bioengineering, Stanford University, Stanford, California, United States of America.
Arvind
A
Kannan
Department of Chemistry, University of Cambridge, Cambridge, United Kingdom; Department of Computer Science, Vrije Universiteit, Amsterdam, The Netherlands.
Maurits J J
MJ
Dijkstra
Department of Computer Science, Vrije Universiteit, Amsterdam, The Netherlands.
Sanne
S
Abeln
Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
Carlo
C
Camilloni
Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
Michele
M
Vendruscolo
D000465:Algorithms; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D011381:Programming Languages; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D012984:Software; D013314:Stress, Mechanical
D011506:Proteins