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.
Papoian
Garegin A
GA
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.
Ulander
Johan
J
Eastwood
Michael P
MP
Luthey-Schulten
Zaida
Z
Wolynes
Peter G
PG
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