A
biophysical theory on the second phase in the
folding of a protein, after the formation of
secondary structure elements, involving the rapid congealing of the protein
hydrophobic core.
Protein folding can be an extremely rapid process (successful folding can happen on the millisecond or microsecond timescale). Given the issue of Levinthal's Paradox, it is surprising a protein folds that quickly, indeed that it ever folds at all. There are two rapid events which contribute to confining the conformational space a protein has to explore during the folding process. The first is the formation of secondary structure - particularly alpha helices and beta hairpins. The backbone hydrogen bonds quickly assemble and form the helical rods. Beta sheets form more slowly as the hydrogen bonds which must be satisfied are often further apart. Sometimes a hairpin can initiate sheet formation.
As the secondary structure elements are being formed, they begin to assemble in a process known as hydrophobic collapse. Due to the hydrophobic effect, which partitions nonpolar residues inside of a protein - the greasy nonpolar sidechains quickly aggregate inside the protein, leaving only polar and charged residues on the outside to interact with water. This rapid and somewhat nonspecific coalescing of nonpolar residues is the collapse event. After collapse, the sidechains then repack more efficiently as they search a limited conformational space in the molten globule state, finally arriving on a stable native state conformation.