The nature of the accessible and buried surfaces in proteins

The accessible surface areas have been calculated for the individual residues in 12 proteins, and for the extended chains, the secondary structures and tertiary structure of six proteins. The results include the following: (1) The formation of α-helices and β-pleated sheets from an extended chain buries a greater proportion of polar surface than non-polar and gives 2 to 3 kcal/mol of hydrophobic free energy per residue. (2) The surfaces buried between the secondary structures are very hydrophobic: being two-thirds non-polar and having more than half the polar part formed by groups that hydrogen bond within their own piece of secondary structure, or which are partially accessible to the solvent. (3) As the six proteins increase in molecular weight they bury an increasing proportion of their non-polar surface (60 to 79%), but a constant proportion of their polar surface (75%). The implications of these results for the theory of protein structure are discussed. In the Appendix it is shown that the accessible surface area of folded proteins is simply proportional to the two-thirds power of their molecular weight.