Molecular descriptors atom-pair

In addition to looking for data trends in physical property space using PCA and PLS, trends in chemical structure space can be delineated by viewing nonlinear maps (NLM) of two-dimensional structure descriptors such as Unity Fingerprints or topological atom pairs using tools such as Benchware DataMiner [42]. Two-dimensional NLM plots provide an overview of chemical structure space and biological activity/molecular properties are mapped in a 3rd and/or 4th dimension to look for trends in the dataset. 

Chemical Information, Irvine CA Tripos, Inc. St. Louis MO), similarity searching can be carried out around a well-defined compound class using local descriptors such as atom pairs [46, 47] or topomeric shape [48, 49]. Also, ligand-based pharmacophore searches are able to identify follow-up compounds that are less obvious and more diverse than similarity searches [30, 50-54]. The problem with the latter methods is defining the molecular shape or pharmacophore specifically enough to be useful when there are few hits within a compound class and they cannot be reliably aligned (as is often the case for NMR hits in the absence of detailed structural information). 

The work of Schneider et al. [6] first focused on the scaffold-hopping ability of autocorrelation descriptors, in this case topological pharmacophores. The general description of the atoms with pharmacophore atom types in combination with the decomposition of molecules into atom pairs was shown to be especially successful in finding new molecules with significant different molecular scaffolds, maintaining the desired biological effect. 

The idea of using atom pairs as molecular features in structure-activity studies vas first proposed by Carhart et al. (84). AP descriptors are defined by their atom types and topological distance bins. An AP is a substructure defined by two atom types and the shortest path separation (or graph distance) between the atoms. The graph distance is defined as the smallest number of atoms along the path connecting two atoms in a molecular structure. The general form of an atom-pair descriptor is as follows ... 

Step 1. Multiple descriptors such as molecular connectivity indices or atom pair descriptors (cf Section 2.1) are generated initially for every compound in a data set. 

A molecular descriptor calculated as the average of the charge differences over all i-j bonded atom pairs ... 

The general RDF can be easily transformed to a basic molecular descriptor by applying it to the 3D coordinates of the atoms in a molecule. In molecular terms, is the distance between the atoms i and j in an Ai-atomic molecule. g r) is usually calculated for all unique pairs of atoms (denoted by i and j) in a certain distance range divided into eqnidistant intervals. Thus, the function g(r) is usually represented by its discrete form of an n-dimensional vector [ (rj), gir ),-, (rn)] calculated between and r . In this case, the RDF is considered as a molecular descriptor (RDF descriptor) for the three-dimensional arrangement of atoms in a molecule. 

Molecular Descriptors are calculated for all pairs of atoms denoted and cover the entire molecule. 

The intrinsic state of an atom can be simply thought of as the ratio of it and lone-pair electrons over the count of the g bonds in the molecular graph for the atom considered. Therefore, the intrinsic state reflects the possible partitioning of non-0 electron s influence along the paths starting from the considered atom the less partitioning of the electron influence, the more available are the valence electrons for intermolecular interactions. The sum of the intrinsic states of all of the atoms is a molecular descriptor called intrinsic state sum moreover, from the intrinsic state sum the —> Q polarity index was derived. 

These are simple molecular descriptors based on counting the defined elements of a compound. The most common chemical count descriptors are —> atom number A, —> bond number B, cyclomatic number C, hydrogen-bond acceptor number, and —> hydrogen-bond donor number, distance-counting descriptors, —> path counts, —> walk counts, atom pairs, and other related —> substructure descriptors. 

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