Consensus preferred hydration sites in six FKBP12-drug complexes.
A set of consensus hydration sites for the FK506-FKBP12 complex are derived by comparing six FKBP12-drug complexes. These hydration sites include a subset of the observed water molecules plus some sites that are occupied by neighboring protein atoms in the FK506-FKBP12 crystal structure. Two hydration prediction algorithms, AUTO-SOL and AQUARIUS2, showed significant increases in apparent efficacy using these consensus water sites, suggesting that our proposed set of consensus hydration sites is truly a better representation of the hydration properties of FKBP12 in solution. Predictably, the consensus hydration sites include all buried water molecules. Otherwise, the features of solvation sites included in the consensus list versus those discarded reveal no distinctive features that would allow them to be selected unambiguously without reference to multiple crystal forms. We suggest that analyses such as this one are a crucial prelude to any theoretical analysis aimed at understanding hydration properties.
Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, New York 14853, USA.
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Faerman
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Karplus
D000465:Algorithms; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011090:Polyenes / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D020123:Sirolimus; D016559:Tacrolimus / Q000737:chemistry / Q000378:metabolism; D022021:Tacrolimus Binding Proteins; D014867:Water / Q000737:chemistry / Q000378:metabolism
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D011090:Polyenes; D011506:Proteins; D014867:Water; D022021:Tacrolimus Binding Proteins; D020123:Sirolimus; D016559:Tacrolimus