title: Residue depth: a novel parameter for the analysis of protein structure and stability.
abstract: BACKGROUND
  Accessible surface area is a parameter that is widely used in analyses of protein structure and stability. Accessible surface area does not, however, distinguish between atoms just below the protein surface and those in the core of the protein. In order to differentiate between such buried residues we describe a computational procedure for calculating the depth of a residue from the protein surface.
  
  
  RESULTS
  Residue depth correlates significantly better than accessibility with effects of mutations on protein stability and on protein-protein interactions. The deepest residues in the native state invariably undergo hydrogen exchange by global unfolding of the protein and are often significantly protected in the corresponding molten-globule states.
  
  
  CONCLUSIONS
  Depth is often a more useful gage of residue burial than accessibility. This is probably related to the fact that the protein interior and surrounding solvent differ significantly in polarity and packing density. Hence, the strengths of van der Waals and electrostatic interactions between residues in a protein might be expected to depend on the distance of the residue(s) from the protein surface.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
authors.forename: S
authors.initials: S
authors.lastname: Chakravarty
authors.forename: R
authors.initials: R
authors.lastname: Varadarajan
mesh_terms: D000577:Amides / Q000737:chemistry; D019943:Amino Acid Substitution; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D000577:Amides