Effects of surface-to-volume ratio of proteins on hydrophilic residues: Decrease in occurrence and increase in buried fraction

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11 Citations (Scopus)


The size of a protein is an important factor for understanding the sequence-structure relationship, and it affects both the amino acid composition and the residue burial of proteins. However, it is usually measured as the number of amino acids, although these effects would result from the reduction of surface regions relative to the volume of core regions in larger proteins. In addition, although these two effects are dependent on each other, they have been studied separately. In this study, we investigated them by considering the surface-to-volume ratio (SVR), and observed the correlation between them. We found that the reduction of several hydrophilic residues is more strongly correlated with SVR than with protein size (the number of amino acids) and that SVR directly affects the amino acid composition. The difference as a descriptor between SVR and size is also supported by the observation that the secondary structural elements correlate completely differently with SVR and with size. Furthermore, for the four most hydrophilic residues, glutamine, arginine, glutamic acid, and lysine, balances between the decrease in composition and the increase in core burial were observed. We found that the burial of glutamine and arginine became accelerated at SVR = 0.3 Å-1 (approximately 132 residues) as the protein size increased, but that lysine has an upper limit of 0.9% for its occurrence in the core. The uniqueness of lysine was also elucidated by comparison with the burial environments of the four hydrophilic residues. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish
Pages (from-to)1596-1602
Number of pages7
JournalProtein Science
Issue number9
Publication statusPublished - 2008 Sep
Externally publishedYes


  • Amino acid propensity
  • Domain size
  • Hydrophobicity
  • Protein structure
  • Surface-to-volume ratio

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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