Molecular properties similarity searching

CAS has developed a molecular property similarity search capability that will allow the rapid scanning of millions of substances with good precision. The technique can be combined with other techniques such as topological similarity searching to provide more of a structure focus or it can act as a screening step for a subsequent, more computationally intensive technique to accomplish, for example, electrostatic similarity. 

Our molecular property similarity searching involves the fuzzy numeric matching of a query and file substance molecular properties. Figure 42 illustrates a target molecule. 

To obtain some insight on whether or not molecular property similarity searching can locate new substance classes for a given use in its own right, the uses as indicated on the STN CA File were examined for the top-ranked molecular property search answers which were NOT top-ranked topological similarity answers on the search database. 

The main conclusion from our study on molecular property similarity searching is that it is useful for discovering new substance classes for a bioactivity, assuming the. same basic mode of action as the query substance. It seems to be effective even though only one low energy conformer is the basis... 

Figure 42 Illustration of molecular property similarity searching...

Similarity search appears as an extremely useful tool for computer-aided structure elucidation as well as for molecular design. Here the similarity property principle is involved. This may be stated as ... 

Multivariate data analysis usually starts with generating a set of spectra and the corresponding chemical structures as a result of a spectrum similarity search in a spectrum database. The peak data are transformed into a set of spectral features and the chemical structures are encoded into molecular descriptors [80]. A spectral feature is a property that can be automatically computed from a mass spectrum. Typical spectral features are the peak intensity at a particular mass/charge value, or logarithmic intensity ratios. The goal of transformation of peak data into spectral features is to obtain descriptors of spectral properties that are more suitable than the original peak list data. 

Downs G M, P Willett and W Fisanick 1994. Similarity Searching and Qustering of Chemical Structure Databases using Molecular Property Data, journal of Chemical Information and Computer Sciences 34 1094-1102. 

Molecular similarity is also useful in predicting molecular properties. Programs that predict properties from a database usually hrst search for compounds in the database that are similar to the unknown compound. The property of the unknown is probably close in value to the property for the known... 

The final part is devoted to a survey of molecular properties of special interest to the medicinal chemist. The Theory of Atoms in Molecules by R. F.W. Bader et al., presented in Chapter 7, enables the quantitative use of chemical concepts, for example those of the functional group in organic chemistry or molecular similarity in medicinal chemistry, for prediction and understanding of chemical processes. This contribution also discusses possible applications of the theory to QSAR. Another important property that can be derived by use of QC calculations is the molecular electrostatic potential. J.S. Murray and P. Politzer describe the use of this property for description of noncovalent interactions between ligand and receptor, and the design of new compounds with specific features (Chapter 8). In Chapter 9, H.D. and M. Holtje describe the use of QC methods to parameterize force-field parameters, and applications to a pharmacophore search of enzyme inhibitors. The authors also show the use of QC methods for investigation of charge-transfer complexes. 

Key Words Chemical database compound selection library design molecular diversity molecular similarity neighborhood behavior similar property principle similarity searching. 

The first application of a surface-based pharmacophore correlation vector was reported by Stiefl and Baumann in 2003 [18] with the MaP (mapping property distributions of molecular surfaces) descriptor. They applied their MaP descriptor for QSAR applications. To our knowledge, an application of this descriptor to similarity searching has not been reported. 

Downs GM, Willett P, Fisanick W, Similarity searching and clustering of chemical-structure databases using molecular property data, J. Chem. Inf. Comput. Sci., 34 1094-1102, 1994. 

Similarity Searching and Clustering of Chemical-Structure Databases Using Molecular Property Data. 

A QSAR approach based on a set of methods that combines molecular shape similarity and commonality measures with other - molecular descriptors both to search for similarities among molecules and to build QSAR models [Hopfinger, 1980 Burke and Hopfinger, 1993], The term molecular shape similarity refers to molecular similarity on the basis of a comparison of three-dimensional molecular shapes represented by some property of the atoms composing the molecule, such as the van der Waals spheres. TTie molecular shape commonality is the measure of molecular similarity when conformational energy and molecular shape are simultaneously considered [Hopfinger and Burke, 1990]. 

Baumann, K. (1999). Uniform-Length Molecular Descriptors for Quantitative Structure-Property Relationships (QSPR) and Quantitative Structure-Activity Relationships (QSAR) Classification Studies and Similarity Searching. TRAC, 18,36-46. 

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