Solvent-induced forces in protein folding reflections on the protein folding problem

•We start with a clear formulation of the protein folding problem.•The so-called “prediction” problem has no general solution.•The solvent induced forces on hydrophilic groups are the strongest ones.•These forces are responsible for the “speed” of the folding process.

It is shown that the solvent induced forces on hydrophilic groups are the strongest ones. The relevance of this finding to protein folding is discussed.

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