PEDS Advance Access published online on November 16, 2009
Protein Engineering Design and Selection, doi:10.1093/protein/gzp069
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The relationship between water bridges and the polyproline II conformation: a large-scale analysis of molecular dynamics simulations and crystal structures
1Biomolecular Structure and Design Program 2Department of Bioengineering, University of Washington, Box 355013, Seattle, WA 98195-5013, USA
3 To whom correspondence should be addressed. E-mail: daggett{at}u.washington.edu
It has been suggested that denatured proteins are predisposed toward the left-handed polyproline II (PII) conformation. One possible source of PII stability in the denatured state is water bridges. Water bridges are networks of water molecules that link nearby hydrogen bond acceptors and/or donors on proteins. On the basis of the proposed behavior of PII and water bridges, the propensity of a residue to participate in water bridges should be correlated with its PII propensity. To test this hypothesis, we analyzed the following data sets: 2351 high-resolution crystal structures, and the native and denatured states of 188 different proteins from all-atom, explicit-solvent molecular dynamics (MD) simulations, which are part of our Dynameomics effort. We found that water bridges do not explain the high frequency of PII in denatured states; such bridges are less frequent around PII than around other conformations. Thus, this analysis casts doubt on water bridges as a dominant factor determining the residue-based PII propensities.
Keywords: coil library/denatured state/molecular dynamics/polyproline II/water bridges
Received October 22, 2009; revised October 22, 2009; accepted October 23, 2009.