Descriptor centers

Figure 1.10 (a) Structure of phenothiazine with descriptor centers marked on it. 

Adapted from ref 41.) (b) Descriptor center cormection graph for phenothiazine. (Adapted from ref. 41.)... 

The chemical structure representation in Apex-3D is based on the concept of a descriptor center that represents a part of the hypothetical biophore. Descriptor centers can be atoms, sets of atoms, pseudo-atoms, or substructures that participate in ligand-receptor interactions. The interaction is derived from electrostatic, hydrophobic, dispersion force, and charge-transfer information that comes from quantum-chemical calculations or from atomic conkibutions to hydrophobicity or molar refractivity. 

A descriptor center finally consists of a structural part (e.g., atom, multiple similar atoms, pseudoatoms, fragments) and a property. To define this structural part efficiently, the line notation SLang is used, which is similar to simplified molecular input line enky specification (SMILES) and SMILES arbitrary target specification (SMARTS) [12]. Examples for structural parts and their representations in SLang are as follows ... 

Descriptor center information for a molecule is stored in a property matrix that contains the indices for all descriptor centers in a molecule and a distance matrix that covers all distances between pairs of descriptor centers. These matrices are finally used to identify the biophores, which then are a subset of the matrices. 

Figure 1 Different representations of a common RNA binding ligand neomycin B. (a) Molecular shape obtained by the calculation of the solvent accessible surface (MSA), (b) Descriptor centers of a pharmacophore corresponding to six-membered rings represented by. spheres in yellow, and nitrogen atoms represented by spheres in cyan, (c) Electrostatic potentials mapped onto an accessible surface. The more electronegative regions are colored in red, the more electropositive regions in blue...

The value of embodies the conformation-independent 3D arrangement of the atoms of the ligands of a chirality center in distance space and thus cannot distinguish between enantiomers. This distinction is introduced by the descriptor S , , . 

An enhancement of the simple substructure approach is the Fragment Reduced to an Environment that is Limited (FREL) method introduced by Dubois et al. [7] With the FREL method several centers of the molecule are described, including their chemical environment. By taking the elements H, C, N, O, and halogens into account and combining all bond types (single, double, triple, aromatic), the authors found descriptors for 43 different FREL centers that can be used to characterize a molecule. 

Using R and S descriptors write al for a molecule with three chirality centers... 

Table 4.36. The NBO descriptors o/ M2H2 species (see Fig. 4.57) namely the accuracy of the natural Lewis structure (%/+). metal charge (Qu), metal hybrid (hM), percentage polarization toward metal (%m), and occupancies (Occ.) of two-center bonds and antibonds...

A comprehensive review on the catalytic performance of josiphos ligands has recently been published [17]. Until now, only the (R, S)-family (and its enantiomers) but not the (R, R) diastereomers have led to high enantioselectivities (the first descriptor stands for the stereogenic center, the second for the planar chirality). The ligands are technically developed, and available in commercial quanti-... 

Three-dimensional (3-D) descriptors of molecules quantify their shape, size, and other structural characteristics which arise out of the 3-D disposition and orientation of atoms and functional groups of molecules in space. A special class of 3-D indices is quantitative descriptors of chirality. If a molecule has one or more chiral centers, the spatial disposition of atoms can produce enantiomers, many of which will have the same magnitude of calculated and experimental physicochemical properties having, at the same time, distinct bioactivity profiles. Basak and coworkers [22] have developed quantitative chirality indices to discriminate such isomers according to their structural invariants which are based on the Cahn-Ingold-Prelog (CIP) rules. 

Once the protein interaction pattern is translated from Cartesian coordinates into distances from the reactive center of the enzyme and the structure of the ligand has been described with similar fingerprints, both sets of descriptors can be compared [25]. The hydrophobic complementarity, the complementarity of charges and H-bonds for the protein and the substrates are all computed using Carbo similarity indices [26]. The prediction of the site of metabolism (either in CYP or in UGT) is based on the hypothesis that the distance between the reactive center on the protein (iron atom in the heme group or the phosphorous atom in UDP) and the interaction points in the protein cavity (GRID-MIF) should correlate to the distance between the reactive center of the molecule (i.e. positions of hydrogen atoms and heteroatoms) and the position of the different atom types in the molecule [27]. 

A from the center of a positive ionizable group was identified. However, its predictive performance on a test set consisted of eight structurally similar compounds was relatively poor. To achieve a computational model with greater predictability, a descriptor-based QSPR model was also developed. Descriptors related to molecular hydrophobicity as well as hydrogen bond donor, shape and charge features contributed to explain hOCTl inhibitor properties of the analyzed compounds. 

The stability of oxygen-centered radicals has been studied repeatedly in recent years in search of quantitative descriptors of antioxidant activity. The antioxidant activity of phenols is indeed so well correlated with O - H BDEs and the ionization potential that these two energies can be used as the guiding... 

---