Fragment-based coding

An improvement of the simple substructure approach is the method fragment reduced to an environment that is limited (FREE) introduced by Dubois et al. [30]. Several centers of the molecule are described, including their chemical environment. By taking the elements H, C, N and O and halogens into account and combining all bond types — single, double, triple, aromatic — the authors found descriptors for 43 different FREE centers that can be used to characterize a molecule. 

To characterize the arrangement of all atoms in a molecule, the entire molecule can be regarded as a connectivity graph where the edges represent the bonds and 

A descriptor for the three-dimensional arrangement of a molecule can be derived from the Cartesian coordinates of the atoms. Reliable coordinates can be calculated quite easily by semiempirical or molecular mechanics (i.e., force-field) methods by using molecular modeling software. Fast 3D structure generators are available that combine rules and force-field methods to calculate Cartesian coordinates from the connection table of a molecule (e.g., CORINA [33]). 

Let us summarize the three important prerequisites for a 3D structure descriptor It should be (1) independent of the number of atoms, that is, the size of a molecule (2) unambiguous regarding the three-dimensional arrangement of the atoms and (3) invariant against translation and rotation of the entire molecule. Further prerequisites depend on the chemical problem to be solved. Some chemical effects may have an undesired influence on the structure descriptor if the experimental data to be processed do not account for them. A typical example is the conformational flexibility of a molecule, which has a profound influence on a 3D descriptor based on Cartesian coordinates. The application in the field of structure-spectrum correlation problems in vibrational spectroscopy requires that a descriptor contains physicochemical information related to vibration states. In addition, it would be helpful to gain the complete 3D structure from the descriptor or at least structural information (descriptor decoding). 

One way to 3D molecular descriptors is deriving them from molecular transforms, which are generalized scattering functions used to create theoretical scattering curves in electron diffraction studies. A molecular transform serves as the functional basis for deriving the relationship between a known molecular structure and x-ray and electron diffraction data. The general molecular transform is 

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Fragment-Based Coding (substructure-based coding) is a code resulting from dividing a molecule into several substructures that represent typical groups. 

A particularly good selection of physical properties may be spectra, because they are known to depend strongly on the chemical structure. In fact, different types of spectra carry different kinds of structural information, NMR spectra characterize individual carbon atoms in their molecular environment. They therefore correspond quite closely to fragment-based descriptors, as underlined by the success of approaches to predict NMR spectra by fragment codes (see Section 10.2.3). 

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