The role of water in protein-DNA recognition

Annu Rev Biophys Biomol Struct. 2004;33:343-61. doi: 10.1146/annurev.biophys.33.110502.140414.


Is it by design or by default that water molecules are observed at the interfaces of some protein-DNA complexes? Both experimental and theoretical studies on the thermodynamics of protein-DNA binding overwhelmingly support the extended hydrophobic view that water release from interfaces favors binding. Structural and energy analyses indicate that the waters that remain at the interfaces of protein-DNA complexes ensure liquid-state packing densities, screen the electrostatic repulsions between like charges (which seems to be by design), and in a few cases act as linkers between complementary charges on the biomolecules (which may well be by default). This review presents a survey of the current literature on water in protein-DNA complexes and a critique of various interpretations of the data in the context of the role of water in protein-DNA binding and principles of protein-DNA recognition in general.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Binding Sites
  • DNA-Binding Proteins / chemistry*
  • Hydrogen Bonding
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Conformation
  • Solvents / chemistry
  • Static Electricity
  • Surface Properties
  • Water / chemistry*


  • DNA-Binding Proteins
  • Solvents
  • Water