Fragment descriptors connectivity

Fragments used for building fragment descriptors can be connected and disconnected. Most applications are based on connected fragments. The point is... 

There are several methods developed for the calculation of logP from molecular structure, based on -> substituent constants, - fragmental constants, - electronic descriptors, -> steric descriptors, - connectivity indices, surface areas, - volume descriptors, and -> chromatographic descriptors [Leo, 1990 Hansch et al., 1995b Carrupt et al., 1997 Reinhard and Drefahl, 1999]. 

Among the -+ graph-invariants, several substituent descriptors have been defined such as, for example, - Kier steric descriptor, - steric vertex topological index and - fragment molecular connectivity indices. 

Fragment descriptors Both two-dimensional (2-D) connection tables for the molecular structures involved, as well as three-dimensional (3-D) information for these structures may generate a variety of fragment descriptors for substructure search systems (for a review of substructure search systems, see Chen ). Active research continues to be carried out in this field, and the interested reader can peruse the review by Downs for more information. 

As illustrated in the next section, the use of biological fingerprints, such as from a BioPrint profile, provides a way to characterize, differentiate and cluster compounds that is more relevant in terms ofthe biological activity of the compounds. The data also show that different in silico descriptors based on the chemical structure can produce quite different results. Thus, the selection of the in silico descriptor to be used, which can range from structural fragments (e.g. MACCS keys), through structural motifs (Daylight keys) to pharmacophore/shape keys (based on both the 2D structure via connectivity and from actual 3D conformations), is very important and some form of validation for the problem at hand should be performed. 

A physical model usually predisposes to physicochemical descriptors, such as p/Ca, log P or molar volume for the whole molecule, or the equivalent descriptors for substituents on a common molecular framework. But different structures can have the same or similar property values, and we are interested in designing structures. So at some stage we must choose structural descriptors (atom types, substructural fragments, connections, or indices from molecular orbital calculations) or at least relate structure to property in order to design the appropriate structure. 

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