text: The main force behind folding is that hydrophobic side chains on some amino acids repel water.  If they are surrounded by water, the system is at a higher energy state than if they are away from water.  Thus, they attact each other, and end up inside the core of the coiled polypeptide chain, with water molecules contacting only charged (polar / ionised) side chains, which end up on the outside.\n\n(This applies to proteins which will be active in aqueous emvironments.  With proteins that will sit in hydrophobic environments, such as in biological membranes, the folding works to keep hydrophobic side chains exposed.)\n\nThen, the positively - charged side chains are attracted to the negatively - charged ones.\n\nFinally, the cysteines that end up near each other may oxidise, turning their -S-H chains into _S_S_ disulfide bridges.  That is; these form late, but then they are stable covalent bonds, and so they do increase the final stability of the 3D folded conformation of the protein.\n\nIt is the 3D structure that gives proteins their biological function.