[Show abstract][Hide abstract] ABSTRACT: General principles of the construction of expert systems for the elucidation of the structure of molecules from their spectra
were considered. The principal attention was focused on systems based on the use of 2-D NMR spectra. The structural information
extracted from 2D NMR spectra was characterized, and the strategy was outlined for structure elucidation under the conditions
when the analyzed spectrostructural information is incomplete, fuzzy, and contradictory. The most advanced expert system ACD/Structure
Elucidator, which is capable of determining the structure and stereochemistry of large molecules, in particular, those typical
in the chemistry of natural compounds, is described as an example.
[Show abstract][Hide abstract] ABSTRACT: The structure of the complex of the antibacterial drug trimethoprim with its target, the enzyme dihydrofolate reductase (DHFR)
of Lactobacillus casei, was studied using multidimensional NMR spectroscopy. Aseries of 33 high-resolution structures of this complex in solution
was calculated using the measured experimental parameters of the nuclear Overhauser effect, spin-spin coupling constants,
and residual dipolar coupling constants. The key interactions leading to stable binding of the drug with the enzyme were determined.
The resulting structural data were compared with structures of the ternary complex of trimethoprim and the coenzyme NADPH
with bacterial (L. casei) and human DHFR that were calculated previously. The most probable reasons for cooperative interaction of trimethoprim and
NADPH that determine the highly selective binding of the drug to the bacterial enzyme, in particular, the protein conformation
change on going from the binary to the ternary complex of DHFR, were discussed.