Water in protein structure prediction.
Proteins have evolved to use water to help guide folding. A physically motivated, nonpairwise-additive model of water-mediated interactions added to a protein structure prediction Hamiltonian yields marked improvement in the quality of structure prediction for larger proteins. Free energy profile analysis suggests that long-range water-mediated potentials guide folding and smooth the underlying folding funnel. Analyzing simulation trajectories gives direct evidence that water-mediated interactions facilitate native-like packing of supersecondary structural elements. Long-range pairing of hydrophilic groups is an integral part of protein architecture. Specific water-mediated interactions are a universal feature of biomolecular recognition landscapes in both folding and binding.
Department of Chemistry and Biochemistry and Center for Theoretical Biological Physics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0371, USA.
Garegin A
GA
Papoian
Johan
J
Ulander
Michael P
MP
Eastwood
Zaida
Z
Luthey-Schulten
Peter G
PG
Wolynes
D019295:Computational Biology; D029968:Escherichia coli Proteins / Q000737:chemistry; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D029968:Escherichia coli Proteins; D011506:Proteins; C084501:hdeA protein, E coli; D014867:Water