Local environment descriptors

In particular, local RDF descriptors are useful for characterizing the chemical environment of an atom and can be applied, for example, to represent the environment of protons in H-NMR spectrum-structure correlations and for the evaluation of steric hindrance at a reaction center. 

Local, or atomic, RDF descriptors are snitable to characterize an individual atom in its chemical environment. They are nsnally not appropriate for investigations of diverse data sets, since each A-atomic molecnle can have N local descriptors. A typical application of local descriptors is the characterization of steric hindrance at reaction centers. This can be performed nsing a conseqnent numbering of the atoms of the reactants. In the following experiment, the Rnthenium atom of each conformer shown in Figure 5.8 was the first atom in the data file, and the local RDF descriptors for atom 1 (Ru) were calculated. Figures 5.10a through 5.10c show the results for the Cartesian RDF descriptors. 

The prediction of chemical shifts in H-NMR spectroscopy is usually more problematic than in C-NMR. Experimental conditions can have an influence on the chemical shifts in H-NMR spectroscopy and structural effects are difficult to estimate. In particular, stereochemistry and 3D effects have been addressed in the context of empirical H-NMR chemical shift prediction only in a few specific situations [81,82]. Most of the available databases lack stereochemical labeling, assignments for diastereo-topic protons, and suitable representations for the 3D environment of hydrogen nuclei [83]. This is the point where local RDF descriptors seemed to be a promising tool. 

Local RDF Descriptor is a geometric descriptor based on radial distribution functions and designed for the characterization of individual atoms in a molecule in their chemical environment. 

Aimed at characterizing the local environment of atoms, these descriptors are calculated by applying the autocorrelation function to encode spatial information relative to each single ith atom in a molecule as [Nohair, Zakarya et al., 2002 Nohair and Zakarya, 2003]... 

MetaDrug incorporates ChemTree 3.1.1 (GoldenHelix). In generating QSAR models a simple descriptor is used, composed of two atoms separated by minimal topological distance between them. The local environment of these atoms is characterized by three values the atomic number, the number of nonhydrogen... 

After the MMPs and their respective contexts and transformations had been generated and stored in the database, several descriptors were employed in order to represent the context of matched molecular pairs. The approach included the consideration of both the local environment around the attachment point and whole molecule/context representations. This division allowed for a hierarchical view of the context representation, starting from the whole molecule and focusing progressively on the well-defined local area where the transformation took place. For the whole molecule representation approach, Murcko frameworks [30] were employed. For the localized approach, atom environments [31] were used. 

Figure 6.6 Examples ofthree context-sensitive the localized atom environment descriptor. The transformations. Dark gray, black, and light gray p-values signify the statistical significance of colors indicate favorable, unfavorable, and zero these observations.The numberofexamples for...

A combination of physicochemical, topological, and geometric information is used to encode the environment of a proton, The geometric information is based on (local) proton radial distribution function (RDF) descriptors and characterizes the 3D environment of the proton. Counterpropagation neural networks established the relationship between protons and their h NMR chemical shifts (for details of neural networks, see Section 9,5). Four different types of protons were... 

Each amino acid has distinct attributes such as size, hydrophobicity/hy-drophilicity, hydrogen bonding capacity, and conformational preferences that allow it to contribute to a protein fold. Attempts are being made to interpret the protein fold in terms of amino acid descriptors. Structural alignments are more accurate than sequence alignments, and the local physicochemical environment of every residue within each 3D structure is directly obtainable (e.g., AAindex at http //www. 

Balaban, A.T. (1995b). Local (Atomic) and Global (Molecular) Graph-Theoretical Descriptors. SAR QSAR Environ.Res., 3,81-95. 

The Cartesian RDF seems to represent the biological activity of the Ruthenium complex. In any case, the descriptor is qnite complex and cannot be compared easily with other molecnles of similar ligand arrangement and with similar biologic potency. Another approach is based on a local descriptor that specifies the chemical environment of the reaction center the Rntheninm atom. 

Averages of local descriptors are useful for recognizing changes in accessible conformations. The moments of the distribution of dihedral angles are an example of such dynamical descriptors. These distributions will vary with the conditions of simulation, such as temperature and molecular environment. 

In practice, often the combination of qualitative SAR analysis with local or global models capturing SAR trends on a more quantitative basis are effective in the design phase for novel derivatives. If these models are based on local chemical environments coupled with interpietable chemical descriptors and preferentially a linear statistical approach for data modeling, those could potentially have a high impact on decisions taken during lead optimization and progressing a project effectively toward the next milestone. 

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