Chemistry Reference
In-Depth Information
The CoMFA method (Cramer et al. 1988) considers the points of the virtual net-
work to be virtual protons and calculates, for each point, steric and electric potentials
that depend on the electrical charge and the van der Waals radii of the atoms of each
molecule.
The PRECLAV program (Tarko 2005) calculates electrostatic forces and paral-
laxes for each point. The parallax is the angle under which a certain pair of atoms is
viewed from the considered point. The maximum and average values of parallaxes
are a measure of the shape and size of the analyzed molecule.
The hypothetical active site lattice (HASL) method (Doweyko 1988) identifies
the points of the network associated to the atoms of the molecule of interest. Then it
gives a fraction of the value of the biochemical property to these points. This frac-
tion is characteristic of the analyzed molecule. By repeating the procedure for all
the molecules in a given set, some points of the network acquire the summing of the
assigned values that are different from null values. These points describe a structure
as a map of the active site of the receptor macromolecule that interacts with the effec-
tor molecules.
4.4 EXAMPLES OF DESCRIPTORS CALCULATION
FOR ORGANOMETALLIC COMPLEXES
When a metal atom ion enters a living organism, it often forms organometallic
complexes in which the ligand is a protein. In many studies, the 3D structure of these
complexes was obtained by X-ray spectroscopy and entered into various databases
such as the Protein Data Bank (n.d.; see, for instance, many ferrodoxins, ferritins,
myelin transcription factors, etc.).
Following are some examples of calculation of descriptors for organometallic
complexes in which the ligand has low molecular weight. Descriptors were chosen
whose values seem to be more sensitive to the presence and type of metal atom, as
well as to the number, shape, and size of ligands. Some of the analyzed complexes
have been synthesized and have various practical applications.
In
Figures 4.9
-4.25, obtained using PCModel (after geometry optimization by
MOPAC), the coordinative chemical bonds are visible only if the calculated value
of the bond order is high enough. To calculate the free valence, we used for V
max
in
Formula (4.10) the value of maximum oxidation states, that is, 2 (for Zn, Mg and
Cd), 3 (for Fe), 4 (for Cu, Ni and Ge), 5 (for Au, Co and V), 6 (for Cr and Pd), and
7 (for Mn).
4.4.1 e
xaMple
1
Figure 4.9 presents the optimized geometry of a hypothetical complex, Cu-glycine
(charge on system = +1). The amino acid has been analyzed in zwitterion state. All
of the heavy atoms are (calculated to be) in the same plane. According to Table 4.1,
the following bonds are identified in the kenograph of the complex: two Cu-O
coordinative bonds, one O-O coordinative bond, two C-O aromatic bonds, one C-C
single bond, and one C-N single bond.
