Proteins are built from a set of twenty different amino acids, chemical building blocks linked together in a specific sequence to form a long chain. What actually determines a protein's function, almost entirely, is its precise three-dimensional shape, and that shape isn't separately specified or built by some additional process; it emerges automatically from the specific sequence of amino acids making up the chain, since each individual amino acid contributes its own distinct chemical character, which collectively determines exactly how the chain folds up.
Each amino acid brings a distinct chemical personality to the chain
The twenty amino acids share a common core structural feature, letting them link together into a chain, but each one carries its own distinct chemical side group attached to that core, giving it a genuinely different chemical character: some are attracted to water, others repelled by it, some carry an electrical charge, others are chemically neutral, and some can form specific chemical bonds with other amino acids elsewhere along the chain. This variation in chemical character is what gives the amino acid sequence its actual functional significance, rather than the sequence being an arbitrary, interchangeable list.
Folding happens automatically as amino acids seek their most stable arrangement
Once a chain of amino acids is assembled, it doesn't stay stretched out in a simple straight line; it folds, quite rapidly and largely automatically, into a specific compact three-dimensional shape, driven by each amino acid's individual chemical tendencies interacting with its neighbours and its surrounding environment. Water-repelling amino acids tend to fold inward, away from the watery environment inside a cell, while water-attracting ones tend to stay on the folded structure's outer surface, and specific chemical bonds between particular amino acids elsewhere in the chain lock the resulting shape into a stable, functional structure, all without needing any separate external process to specify or guide that final shape.
What we're still unsure about
The basic principle that amino acid sequence determines protein folding, and the general chemical forces driving that folding process, are well established, extensively confirmed biochemistry. What remains a genuinely significant, actively worked-on scientific challenge is reliably predicting a protein's exact final folded shape directly from its amino acid sequence alone using computational methods, since the folding process involves an astronomically large number of theoretically possible intermediate shapes, and predicting the correct final structure from sequence data has historically been a difficult computational problem — while recent computational tools have made major, genuinely impressive progress on this prediction problem, it isn't yet fully solved for every possible protein sequence with complete reliability.
This sits inside Amino Acids & Protein Structure, one of seven topics in Biochemistry, one of six domains in Chemistry, one of seventeen subjects the app can quiz you on.