Interior and surface of monomeric proteins

The solvent-accessible surface area (A_s) of 46 monomeric proteins is calculated using atomic co-ordinates from high-resolution and well-refined crystal structures. The A_s of these proteins can be determined to within 1 to 2 % and that of their individual residues to within 10 to 20%. The A_s values of proteins are correlated with their molecular weight (M_r) in the range 4000 to 35,000: the power law A_s = 6.3 M^0.73 predicts protein A_s values to within 4% on average. The average water-accessible surface is found to be 57% non-polar, 24% polar and 19% charged, with 5% root-mean-square variations. The molecular surface buried inside the protein is 58% non-polar, 39% polar and 4% charged. The buried surface contains more uncharged polar groups (mostly peptides) than the surface that remains accessible, but many fewer charged groups. On average, 15% of residues in small proteins and 32% in larger ones may be classed as "buried residues", having less than 5% of their surface accessible to the solvent. The accessibilities of most other residues are evenly distributed in the range 5 to 50%. Although the fraction of buried residues increases with molecular weight, the amino acid compositions of the protein interior and surface show no systematic variation with molecular weight, except for small proteins that are often very rich in buried cysteines. From amino acid compositions of protein surfaces and interiors we calculate an effective coefficient of partition for each type of residue, and derive an implied set of transfer free energy values. This is compared with other sets of partition coefficients derived directly from experimental data. The extent to which groups of residues (charged, polar and non-polar) are buried within proteins correlates well with their hydrophobicity derived from amino acid transfer experiments. Within these three groups, the correlation is low.