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Atomic and residue hydrophilicity in the context of folded protein structures

Academic Article
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Overview

authors

  • Kuhn, L. A.
  • Swanson, C. A.
  • Pique, M. E.
  • Tainer, John
  • Getzoff, Elizabeth

publication date

  • December 1995

journal

  • Proteins-Structure Function and Genetics  Journal

abstract

  • Water-protein interactions drive protein folding, stabilize the folded structure, and influence molecular recognition and catalysis. We analyzed the closest protein contacts of 10,837 water molecules in crystallographic structures to define a specific hydrophilicity scale reflecting specific rather than bulk solvent interactions. The tendencies of different atom and residue types to be the nearest protein neighbors of bound water molecules correlated with other hydrophobicity scales, verified the relevance of crystallographically determined water positions, and provided a direct experimental measure of water affinity in the context of the folded protein. This specific hydrophilicity was highly correlated with hydrogen-bonding capacity, and correlated better with experimental than computationally derived measures of partitioning between aqueous and organic phases. Atoms with related chemistry clustered with respect to the number of bound water molecules. Neutral and negatively charged oxygen atoms were the most hydrophilic, followed by positively-charged then neutral nitrogen atoms, followed by carbon and sulfur atoms. Agreement between observed side-chain specific hydrophilicity values and values derived from the atomic hydrophilicity scale showed that hydrophilicity values can be synthesized for different functional groups, such as unusual side or main chains, discontinuous epitopes, and drug molecules. Two methods of atomic hydrophilicity analysis provided a measure of complementarity in the interfaces of trypsin:pancreatic trypsin inhibitor and HIV protease:U-75875 inhibitor complexes.

subject areas

  • Amino Acids
  • Binding Sites
  • Computer Graphics
  • Computer Simulation
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Models, Molecular
  • Protein Folding
  • Proteins
  • Water
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Research

keywords

  • X-ray crystallography
  • drug and inhibitor design
  • hydration
  • hydrophobicity
  • molecular recognition
  • ordered solvent
  • protein surface analysis
  • solvation
  • water
  • water-protein interactions
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Identity

International Standard Serial Number (ISSN)

  • 0887-3585

Digital Object Identifier (DOI)

  • 10.1002/prot.340230408

PubMed ID

  • 8749849
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Additional Document Info

start page

  • 536

end page

  • 547

volume

  • 23

issue

  • 4

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