COMPACTNESS DETERMINES PROTEIN FOLDING TYPE

Abstract

We have demonstrated here that protein compactness, which we define as the ratio of the accessible surface area of a protein to that of the ideal sphere of the same volume, is one of the factors determining the mechanism of protein folding. Proteins with multi-state kinetics, on average, are more compact (compactness is 1.49 ± 0.02 for proteins within the size range of 101–151 amino acid residues) than proteins with two-state kinetics (compactness is 1.59 ± 0.03 for proteins within the same size range of 101–151 amino acid residues). We have shown that compactness for homologous proteins can explain both the difference in folding rates and the difference in folding mechanisms.