Protein structure can be viewed at four levels: I) Primary Structure: The amino acid sequence of a protein. II) Secondary Structure: Motifs which sections of a sequence organize themselves into. These are mainly alpha helices and beta sheets. III) Tertiary Structure: The overall structure of a single polypeptide. IV) Quaternary Structure: The way that two or more polypeptides join to form a single unit. (Not all proteins have a quaternary structure since many polypeptides function solo.)
The main question posed by the protein folding problem is "Can the final folded structure of a protein be predicted from its amino acid sequence?" In other words, given the primary structure, can the higher order structures be predicted. So, far there has been limited success with predicting portions of the secondary structure based on amino acid sequence. For instance, certain amino acid sequences are recognized as likely to fold into various motifs. Success in predicting tertiary structure has been even more limited. Further complicating this problem is that many proteins require the help of other proteins (molecular chaperones) to fold into their proper conformation.
Certain amino acids form attachments to other amino acids. Certain amino acids repel certain other amino acids. How do the right amino acids wind up attached to their corresponding amino acids? If the wrong amino acids wind up attached to other attractive, but inappropriate amino acids a nonfunctional conformation will be achieved. For a protein to function properly it must attain its proper conformation, otherwise it is just a tangled, useless mess!