Dynamics of hydrogen bond desolvation in protein folding

J Mol Biol. 2002 Aug 23;321(4):659-75. doi: 10.1016/s0022-2836(02)00679-4.


As proteins fold, a progressive structuring, immobilization and eventual exclusion of water surrounding backbone hydrogen bonds takes place. This process turns hydrogen bonds into major determinants of the folding pathway and compensates for the penalty of desolvation of the backbone polar groups. Taken as an average over all hydrogen bonds in a native fold, this extent of protection is found to be nearly ubiquitous. It is dynamically crucial, determining a constraint in the long-time limit behavior of coarse-grained ab initio simulations. Furthermore, an examination of one of the longest available (1micros) all-atom simulations with explicit solvent reveals that this average extent of protection is a constant of motion for the folding trajectory. We propose how such a stabilization is best achieved by clustering five hydrophobes around the backbone hydrogen bonds, an arrangement that yields the optimal stabilization. Our results support and clarify the view that hydrophobic surface burial should be commensurate with hydrogen-bond formation and enable us to define a basic desolvation motif inherent to structure and folding dynamics.

MeSH terms

  • Algorithms
  • Carrier Proteins / chemistry
  • Computer Simulation
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • Microfilament Proteins / chemistry
  • Models, Molecular
  • Motion
  • Nerve Tissue Proteins / chemistry
  • Protein Conformation
  • Protein Folding*
  • Proteins / chemistry*
  • Proteins / metabolism
  • Solvents
  • Thermodynamics


  • Carrier Proteins
  • G-substrate
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Proteins
  • Solvents
  • villin