CONSENSUS PREFERRED HYDRATION SITES IN 6 FKBP12 DRUG COMPLEXES

A set of consensus hydration sites for the FK506-FKBP12 complex are de rived by comparing six FKBP12-drug com complexes, These hydration site s include a subset of the observed water molecules plus some sites tha t are occupied by neighboring protein atoms in the FK506-FKBP12 crysta l structure, Two hydration prediction algorithms, AUTO-SOL and AQUARIU S2, showed significant increases in apparent efficacy using these cons ensus water sites, suggesting that our proposed set of consensus hydra tion sites is truly a better representation of the hydration propertie s of FKBP12 in solution, Predictably, the consensus hydration sites in clude 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 unambiguous ly without reference to multiple crystal forms, We suggest that analys es such as this one are a crucial prelude to any theoretical analysis aimed at understanding hydration properties. (C) 1995 Wiley-Liss, Inc.