Novel Molecular Descriptors

Do we still need additional molecular descriptors Well, there will always be room for new and novel molecular descriptors that will incorporate some structural information that has not been well captured by current molecular descriptors. But these days, novel molecular descriptors are hard to find, particularly if they are to be conceptually and computationally simple and have straightforward structural interpretation. Finding such will continue to be not an everyday event. However, recall a statement of E. Bright Wilson [1] ... every once in a while some new theory or new experimental method or apparatus makes it possible to enter a new domain.  

One such new theory has been the common vertex matrix [2], which has led to a novel approach to graph eccentricities and network eccentricities, based on the count of pairs of vertices at equal distance from each vertex in a graph [3]. A preliminary study has shown that the connectivity-type index based on the vertex centrality values displays considerable discriminatory power in differentiating between similar structures, including very similar structures among isomers. The discriminatory power of a centrality-based connectivity index exceeds visibly the discriminatory power of Balaban s J index [4-6], which is a distance matrix analog of the connectivity index. 

It does appear that novel matrices of graphs, such as, for example, the recently constructed -dimensional (pseudo) distance matrix [7], the D ax matrix containing only the maximal distances in each row and each column of the distance matrix [8,9], and the already mentioned common vertex matrix [2], may lead to a number of novel graph descriptors, some of which may be of interest in the search for structurally highly similar molecules. 

Although some may view the continuing interest of a number of scientists in construction of novel indices, when there are thousands that have been already introduced, as a violation of the Occam s razor doctrine, one should not overlook another doctrine that characterizes the importance of scientific results, which says the importance of novelty can be measured by the number of existing items it makes irrelevant. This comes from David Hilbert (1862-1943), a very distinguished German mathematician at the turn of the century, whose exact words are, One can measure the importance of a scientific work by the number of earlier publications rendered superfluous by it.  

From that point of view, new mathematical descriptors of recent times are more likely than not to make many ad hoc descriptors of the past less relevant for QSAR than they appear today. 

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Pearlman [22] has developed novel molecular descriptors called BCUT values for use in diversity studies. They are designed to combine atomic properties with connectivity information in order to define a low-... 

Randic, M. (1993c). Novel Molecular Descriptor for Structure-Property Studies. Chem.Phys. Lett., 277,478-483. 

To make the Szeged index of compounds with odd member rings to be of comparable magnitude with that of compounds containing even member rings, Randic proposed to calculate the Szeged index by also taking into account contributions from atoms at the same distance from the atoms at both ends of a bond. This led to a novel molecular descriptor, which... 

Pearlman [24] has developed novel molecular descriptors that are called BCUT values. These can be used to define a low-dimensional chemistry space. 

M. Randid, Novel molecular descriptor for structure-property studies, Chem. Phys. Lett. 211 (1993)478-483. 

Summation of nonzero elements in the upper or lower matrix-triangles gives the Wiener index (Wiener number). The edge-Wiener matrix was also found to be a rich and stimulating source of novel molecular descriptors (Randid et al., 1993, 1994 Lucid et al., 2003). 

With this, we would like to end the introduction into justification for searching for novel molecular descriptors specifically designed for searching combinatorial libraries and highly similar structures. We hope that this may alert researchers looking for novel drugs to discuss this problem and, despite a few additional applications. 

Pastor, M., Cruciani, G., McLay, L, Pickett, S., Glementi, S. GRid-INdependent descriptors (GRIND) a novel class of alignment-independent three-dimensional molecular descriptors. /. Med. Chem. 2000, 43, 3233-3243. 

Calculated molecular properties from 3D molecular fields of interaction energies are a novel approach to correlate 3D molecular structures with pharmacodynamic, pharmacokinetic and physico-chemical properties. The novel VolSurf descriptors quantitatively characterize size, shape, polarity, hydrophobicity and the balance between them. 

Golbraikh, A., Bonchev, D., Tropsha, A. Novel chirality descriptors derived from molecular topology. J. Chem. Inf. Comput. Sci. 2001, 41, 147-158. 

Horvath D. (2001b) ComPharm—Automated comparative analysis of phar-macophoric patterns and derived QSAR approaches, novel tools in high throughput drug discovery. A proof-of-concept study applied to farnesyl protein transferase inhibitor design. In M Diudea (ed), QSPR/QSAR Studies by Molecular Descriptors, pp. 395-439, Nova Science Publishers, New York, USA. 

Brown WM, Martin S, Rintoul MD et al. (2006) Designing novel polymers with targeted properties using the signature molecular descriptor. J Chem Inf Model 46 826-835... 

Melagraki G, Afantitis A, Sarimveis H et al. (2007) A novel QSPR model for predicting theta (lower critical solution temperature) in polymer solutions using molecular descriptors. J Mol Model 15 55-64... 

Daneshtalab M (2006) Novel Synthetic Antibacterial Agents. 2 153-206 Duchowicz PR, Castro EA, Toropov AA, Benfenati E (2006) Applications of Flexible Molecular Descriptors in the QSPR-QSAR Study of Heterocyclic Drugs. 3 1-38... 

Pastor M, Cruciani G, McLay I et al. (2000) Grid-independent descriptors (GRIND) A novel class of alignment-independent Three-dimensional molecular descriptors. J Med Chem 43 3233-3243... 

In addition, there have also been a number of efforts to find more efficient ways to categorise and enumerate compounds. One approach to defining the relationship of compounds to each other uses a chemical space defined by a set of 500 compounds described with 60 molecular descriptors onto which novel compounds can then be mapped.116 Another approach that has been described uses a rule-based classification scheme to define the common scaffold or core of compounds.117 This approach has been taken further to develop a scoring function to allow the prioritisation of compound libraries for testing.118... 

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