Modeling Protein–Protein
Recognition in Solution
Using the Coarse-Grained Force Field SCORPION
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Abstract
We present here the SCORPIONSolvated COaRse-grained
Protein
interactIONforce field, a physics-based simplified coarse-grained
(CG) force field. It combines our previous CG protein model and a
novel particle-based water model which makes it suitable for Molecular
Dynamics (MD) simulations of protein association processes. The protein
model in SCORPION represents each amino acid with one to three beads,
for which electrostatic and van der Waals effective interactions are
fitted separately to reproduce those of the all-atom AMBER force field.
The protein internal flexibility is accounted for by an elastic network
model (ENM). We now include in SCORPION a new Polarizable Coarse-Grained
Solvent (PCGS) model, which is computationally efficient, consistent
with the protein CG representation, and yields accurate electrostatic
free energies of proteins. SCORPION is used here for the first time
to perform hundreds-of-nanoseconds-long MD simulations of protein/protein
recognition in water, here the case of the barnase/barstar complex.
These MD simulations showed that, for five of a total of seven simulations
starting from several initial conformations, and after a time going
from 1 to 500 ns, the proteins bind in a conformation very close to
the native bound structure and remain stable in this conformation
for the rest of the simulation. An energetic analysis of these MD
show that this recognition is driven both by van der Waals and electrostatic
interactions between proteins. SCORPION appears therefore as a useful
tool to study protein–protein recognition in a solvated environment