Bend a chain of residues across a grid so the hydrophobic units huddle into a buried core, and squeeze the energy down to its proven minimum.
A protein is modelled as a chain of hydrophobic (H) and polar (P) residues on a 2D lattice. Hydrophobic neighbours that sit adjacent without being bonded lower the energy. Your goal is to fold the chain so the H residues form a compact core and you hit the optimum energy.
Helixfold is built on the classic hydrophobic-polar lattice model of protein folding, turning the search for a fold into a puzzle.
A chain of hydrophobic and polar residues on a lattice, where non-bonded H-H contacts lower the energy, is the HP model of protein folding.
Scoring energy directly, rather than similarity to a known shape, is the original approach.
Energy is the right objective because it is what nature minimises. The hydrophobic effect drives nonpolar residues inward, and a model containing little else still reproduces the compact core real proteins have — which is why the HP model survives as a teaching and research tool.
Helixfold is built on the classic hydrophobic-polar lattice model of protein folding, turning the search for a minimum-energy conformation into a tactile puzzle. It's an original, free browser game with three chain lengths and daily plus practice modes.