title: Anatomy by computer experiment of the exchange of a water molecule buried in human apolipoprotein E.
abstract: BACKGROUND
  NMR experiments show that even water molecules that are well ordered in a crystal structure exchange with the external solvent. Despite crucial progress on the understanding of the exchange of crystal-buried water molecules, the detailed pathways followed by a water molecule to escape from or penetrate into the protein interior are unknown.
  
  
  RESULTS
  The exchange of a crystal water molecule buried in the low-density lipoprotein receptor-binding domain of human apolipoprotein E with a water molecule from the external solvent was detected and monitored in a molecular dynamics simulation. This simulation shows that the escape of the crystal water molecule from the protein interior and the penetration of the water molecule from the bulk occur by a single-pathway mechanism involving conformational fluctuations of arginine and tryptophan sidechains. Along the pathway the exchanging water molecule interacts specifically with protein atoms by way of a varying pattern of hydrogen bonds.
  
  
  CONCLUSIONS
  The exchange pathway revealed by the molecular dynamics trajectory suggests a mechanism by which hydrogen bonds work in relay to permit either the penetration or the expulsion of a water molecule. This result may have important implications not only on the process of water exchange but also to probe ligand binding to proteins.
authors.affiliation: Ingénierie Biomoléculaire, Université Libre de Bruxelles, CP 165, Av.F. Roosevelt, B-1050, Bruxelles, Belgium. mprevost@ulb.ac.be
authors.forename: M
authors.initials: M
authors.lastname: Prévost
mesh_terms: D001057:Apolipoproteins E / Q000737:chemistry*; D003198:Computer Simulation; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D011487:Protein Conformation; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D001057:Apolipoproteins E; D014867:Water