Hydrophobicity and residue-residue contacts in globular proteins

A comprehensive statistical analysis of residue-residue contacts and residue environment in protein 3-D structures is presented. In the present work the range of interresidue interactions (effective radius of influence) in tertiary structures of proteins is examined and found to be 10 A. This result is obtained by correlating the average number of residues within a spherical volume of different radii (contact numbers) with hydrophobicity. Best correlations are obtained with a radius of 10 A. The same result is obtained when (i) only long-range interactions are considered and (ii) representative side chain atoms are used to indicate the tertiary structure instead of the usual representation of Cα atoms. Residue environment has been investigated using similar methods. Environmental hydrophobicity varies within only a small range of all residue types. Other physicochemical properties also exhibit similar trends of variation, and only five hydrophobic residues (Leu, Val, Met, Phe and Ile) produce a decrement of around 10% from the expected mean of the physicochemical distance between a residue type and its average environment. An information theory approach is proposed to compare domains, which takes into account the effective radius of influence of residues and sequence similarity.