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Evidence of Water MoleculesA Statistical Evaluation of Water Molecules Based on Electron Density
journal contribution
posted on 2015-04-27, 00:00 authored by Eva Nittinger, Nadine Schneider, Gudrun Lange, Matthias RareyWater
molecules play important roles in many biological processes,
especially when mediating protein–ligand interactions. Dehydration
and the hydrophobic effect are of central importance for estimating
binding affinities. Due to the specific geometric characteristics
of hydrogen bond functions of water molecules, meaning two acceptor
and two donor functions in a tetrahedral arrangement, they have to
be modeled accurately. Despite many attempts in the past years, accurate
prediction of water moleculesstructurally as well as energeticallyremains
a grand challenge. One reason is certainly the lack of experimental
data, since energetic contributions of water molecules can only be
measured indirectly. However, on the structural side, the electron
density clearly shows the positions of stable water molecules. This
information has the potential to improve models on water structure
and energy in proteins and protein interfaces. On the basis of a high-resolution
subset of the Protein Data Bank, we have conducted an extensive statistical
analysis of 2.3 million water molecules, discriminating those water
molecules that are well resolved and those without much evidence of
electron density. In order to perform this classification, we introduce
a new measurement of electron density around an individual atom enabling
the automatic quantification of experimental support. On the basis
of this measurement, we present an analysis of water molecules with
a detailed profile of geometric and structural features. This data,
which is freely available, can be applied to not only modeling and
validation of new water models in structural biology but also in molecular
design.