  Water molecules and molecular chaperones efficiently help the protein folding
process. Here we describe their action in the context of the energy and
topological networks of proteins. In energy terms water and chaperones were
suggested to decrease the activation energy between various local energy minima
smoothing the energy landscape, rescuing misfolded proteins from conformational
traps and stabilizing their native structure. In kinetic terms water and
chaperones may make the punctuated equilibrium of conformational changes less
punctuated and help protein relaxation. Finally, water and chaperones may help
the convergence of multiple energy landscapes during protein-macromolecule
interactions. We also discuss the possibility of the introduction of protein
games to narrow the multitude of the energy landscapes when a protein binds to
another macromolecule. Both water and chaperones provide a diffuse set of
rapidly fluctuating weak links (low affinity and low probability interactions),
which allow the generalization of all these statements to a multitude of
networks.
