Bury the water-fearing residues together and watch the energy drop.
You're given a chain of residues, some hydrophobic (H) and some not. Fold it on the grid so the hydrophobic residues cluster into a buried core, each non-adjacent H-H pair that ends up touching lowers the structure's energy. Reach the lowest energy to solve it.
Protein Fold is a biochemistry puzzle built on how proteins fold around a hydrophobic core, the principle that gives proteins their shape.
Folding a chain of hydrophobic and polar residues so the hydrophobic ones bury into a core, scoring each non-adjacent H-H contact, is the HP lattice model of protein folding.
Scoring the buried contacts directly is the original simplification.
It is a drastic simplification that keeps the essential physics. The hydrophobic effect — nonpolar groups aggregating because that maximises the entropy of the surrounding water — is the dominant force driving a protein into shape, so a model with almost nothing else in it still produces recognisably protein-like folds.
Protein Fold is a biochemistry puzzle built around hydrophobic-core protein folding models. It's an original, free browser game made in-house for PlayPendium.