Chemistry Reference
In-Depth Information
on the basis of high-resolution X-ray measurements of the pure compound might
give wrong results.
The computations indicate that gas phase results often deviate quite strongly
from the corresponding crystal or enzyme-inhibitor complex data. The agreement
improves if the geometrical arrangement of the inhibitor-enzyme complex is used
for the gas phase calculations, but the deviations are still considerable. A much
better approximation is obtained if the environmental effects are mimicked by the
influence of a polar solvent via continuum models. The resulting EDs include
polarizations which approximate the situation in crystals or enzyme-inhibitor
complexes very well as long as the geometries do not differ too much. Deviations
between the less expensive COSMO computation and the QM/MM calculations are
often smaller than 1% if the computation is performed for the geometrical structure,
which the inhibitor adopts in the crystal of the pure compound or in the inhibitor-
enzyme complex. Hence, the former approach would be very useful for databases of
average multipole populations or aspherical atomic density functions.
Finally, the Source Function descriptor was scrutinized for its potential to
disentangle the effect of the environment on the charge density distribution of the
inhibitor species. A preliminary investigation on hydrocarbon linkages and water
clusters of increasing size showed that the inclusion of the second neighbors in the
QM part allows replicating the effects of the surrounding on the ED features of
typical covalent or hydrogen bonded interactions.
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