A ?solvated rotamer? approach to modeling water-mediated hydrogen bonds at protein-protein interfaces

@article{citeulike:698444, abstract = {Water-mediated hydrogen bonds play critical roles at protein-protein and protein-nucleic acid interfaces, and the interactions formed by discrete water molecules cannot be captured using continuum solvent models. We describe a simple model for the energetics of water-mediated hydrogen bonds, and show that, together with knowledge of the positions of buried water molecules observed in X-ray crystal structures, the model improves the prediction of free-energy changes upon mutation at protein-protein interfaces, and the recovery of native amino acid sequences in protein interface design calculations. We then describe a ?solvated rotamer? approach to efficiently predict the positions of water molecules, at protein-protein interfaces and in monomeric proteins, that is compatible with widely used rotamer-based side-chain packing and protein design algorithms. Finally, we examine the extent to which the predicted water molecules can be used to improve prediction of amino acid identities and protein-protein interface stability, and discuss avenues for overcoming current limitations of the approach. Proteins 2005. {\copyright} 2005 Wiley-Liss, Inc.}, address = {Department of Biochemistry, University of Washington, Seattle, Washington; Biomolecular Structure \& Design Program, University of Washington, Seattle, Washington}, author = {Jiang, Lin and Kuhlman, Brian and Kortemme, Tanja and Baker, David }, citeulike-article-id = {698444}, doi = {http://dx.doi.org/10.1002/prot.20347}, journal = {Proteins: Structure, Function, and Bioinformatics}, keywords = {rosetta}, number = {4}, pages = {893--904}, posted-at = {2007-11-12 17:16:53}, priority = {2}, title = {A ?solvated rotamer? approach to modeling water-mediated hydrogen bonds at protein-protein interfaces}, url = {http://dx.doi.org/10.1002/prot.20347}, volume = {58}, year = {2005} }

TY - JOUR ID - citeulike:698444 L3 - citeulike-article-id:698444 TI - A ?solvated rotamer? approach to modeling water-mediated hydrogen bonds at protein-protein interfaces JF - Proteins: Structure, Function, and Bioinformatics VL - 58 IS - 4 SP - 893 EP - 904 AD - Department of Biochemistry, University of Washington, Seattle, Washington; Biomolecular Structure & Design Program, University of Washington, Seattle, Washington N2 - Water-mediated hydrogen bonds play critical roles at protein-protein and protein-nucleic acid interfaces, and the interactions formed by discrete water molecules cannot be captured using continuum solvent models. We describe a simple model for the energetics of water-mediated hydrogen bonds, and show that, together with knowledge of the positions of buried water molecules observed in X-ray crystal structures, the model improves the prediction of free-energy changes upon mutation at protein-protein interfaces, and the recovery of native amino acid sequences in protein interface design calculations. We then describe a ?solvated rotamer? approach to efficiently predict the positions of water molecules, at protein-protein interfaces and in monomeric proteins, that is compatible with widely used rotamer-based side-chain packing and protein design algorithms. Finally, we examine the extent to which the predicted water molecules can be used to improve prediction of amino acid identities and protein-protein interface stability, and discuss avenues for overcoming current limitations of the approach. Proteins 2005. © 2005 Wiley-Liss, Inc. KW - rosetta AU - Jiang, Lin AU - Kuhlman, Brian AU - Kortemme, Tanja AU - Baker, David PY - 2005/// UR - http://dx.doi.org/10.1002/prot.20347 ER -