Molecular similarity/dissimilarity

Molecular diversity is thus plagued not only with the problems inherent in molecular similarity/dissimilarity [5, 6] but also with those problems associated with molecular populations [7]. One of the foremost problems is that computed molecular similarity values are not invariant to the molecular representation and to the similarity measure used [5]. Nearest-neighbor (NN) relationships, which are employed extensively in many aspects of HTS, are thus problematic, and it is difficult, and in many cases impossible, to obtain consistent subsets [8]. The structure of chemistry space can also be altered significantly in a global sense. As molecular diversity also depends on these factors, it too can be problematic and inconsistencies will no doubt arise. 

Lajiness MS. Applications of molecular similarity/dissimilarity in drug research. In van de Waterbeemd H, editor. Structure-Pmperty Correlation s in Drug Research. Austin R.G. Landes Company 1996. p 179-205. 

Once we have the measures, we have to apply them to chemical objects. Objects of interest to a chemist include molecules, reactions, mbrtures, spectra, patents, journal articles, atoms, functional groups, and complex chemical systems. Most frequently, the objects studied for similarity/dissimilarity are molecular structures. 

Molecular diversity has a relatively brief history, which began in the late eighties and somewhat parallels the development of combinatorial chemistry [1]. Unlike molecular similarity [2-4], which is a pairwise measure, molecular diversity is a measure of the similarity distribution over a population of molecules. Alternatively, molecular diversity can be assessed in terms of the dissimilarity distribution over a population of molecules since the dissimilarity of two molecules i and j is the complement of their similarity, that is D i,j) = 1 — S i,j). 

Key Words Molecular similarity molecular similarity analyses (MSA) dissimilarity. 

Closely allied with the notion of molecular similarity is that of a chemistry space. Chemistry spaces provide a means for conceptualizing and visualizing molecular similarity. A chemistry space consists of a set of molecules and a set of associated relations (e.g., similarities, dissimilarities, distances, and so on) among the molecules, which give the space a structure (8). In most chemistry spaces, which are coordinate-based, molecules are generally depicted as points. This, however, need not always be the case—sometimes only similarities or distances among molecules in the population are known. Nevertheless, this type of pairwise information can be used to construct an appropriate coordinate... 

Other forms for the pseudo-energy penalty term have also been investigated (61,62). In any case, pseudo-energy penalty term acts as a constraint on the overall energy of the system, which is a balance between favorable conformational energies and overall molecular alignment as measured by field-based similarity (dissimilarity). 

Subheading 2.5. provides a very brief discussion of molecular dissimilarity measures that are basically the complement of their corresponding molecular similarity measures. This section also presents reasons as to why similarity is preferred over dissimilarity, except in studies of diversity, as a measure of molecular resemblance. 

Holliday, J. D., Hu, C.-Y., and Willett, P. (2002) Grouping of coefficients for the calculation of inter-molecular similarity and dissimilarity using 2D fragment bit-strings. Combi. Chem. High Through. Screen. 5, 155-166. 

Indices of molecular similarity and dissimilarity based on the electron momentum density have been found useful by Allan, Cooper and coworkers [388-393] and Ho et al. [394]. 

Tel. 218-720-4279, fax 218-720-4219, e-mail sbasak ua.d.umn.edu Generation of connectivity and other molecular descriptors for use in QSAR and similarity/dissimilarity analysis. Silicon Graphics and PCs. 

Similarity/dissimilarity obviously plays an important role in all pattern recognition problems. The vagueness of this term itself suggests that there are numerous ways in which the dissimilarity D of two objects a and b may be defined, depending on the actual problem. Segmentation of molecular... 

Balaban, A.T. (1998). Topological and Stereochemical Molecular Descriptors for Databases Useful in QSAR, Similarity/Dissimilarity and Drug Design. SAR QSAR Environ.Res., 8,1-21. 

Richards, W.G. (1995). Molecular Similarity and Dissimilarity. In Modelling of Biomolecular Structures and Mechanisms (Pullman, A., Jortner, J. and Pullman, B., eds.), Kluwer, Dordrecht (The Netherlands), pp. 365-369. 

An increased interest in molecular similarity (or dissimilarity) has had a beneficial impact on the design of combinatorial chemistry libraries and because of this the diversity of compounds in a library has generally increased. More recently attention has also focused on drug-likeness of libraries (see Section IV.C.). This has brought about a change in the types and increase in the number of descriptors which are used in QSAR studies and this is discussed below. 

It is clear that the particular approach to molecular similarity employed here can be used to rationalise HIVl virology data for the famiUes of phospholipids considered and even to make some successful predictions of active compounds. Preliminary results for various AZT derivatives (reverse transcriptase inhibitors) are also encouraging. The active compounds all feature an -N3 group. Nevertheless, comparisons of the HOMOs, which are localised in the thymine rings, can be used to distinguish easily between active and inactive compounds. Similarly, it has proved possible to identify features that are common to various, structurally-dissimilar, non-nucleoside reverse transcriptase inhibitors. 

Kubinyi H. Similarity and dissimilarity—a medicinal chemist s view. In Kubinyi H, Folkers G, Martin YC, eds. 3D QSAR in Drug Design Vol. 2. Ligand-Protein Complexes and Molecular Similarity. Dordrecht Kluwer/ESCOM, 1998 225-252 also published in Perspect Drug Discov Des 1998 9-11 225-252. 

Balaban AT. Topological and stereochemical molecular descriptors for databases useful in QSAR similarity/dissimilarity and drug design. SAR QSAR Environ Res 1998 8 1-21. 

Molecular similarity The degree of similarity between molecules, although quantitatively measurable, very much depends on what molecular features are used to establish the degree of similarity. One of the many comparators is the electron density of a pair of molecules. Other comparators include electrostatic potentials, reactivity indices, hydrophobicity potentials, molecular geometry such as distances and angles between key atoms, solvent accessible surface area, etc. It is an open question as to how much or what part(s) of the molecular structure is to be compared. The Tanimoto coefficient which compares dissimilarity to similarity is often used in molecular diversity analysis. 

We will take the paths of Table 1 as molecular descriptors to obtain a quantitative measure of molecular similarity. In Table 2 we show the similarity/dissimilarity table for the octane isomers using the Euclidean distance as the measure of similarity. The smaller entries in Table 2 indicate molecules found similar under the procedure adopted, while the larger entries point to the least similar structures. 

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