Similarity molecular

These fingerprints can be used to calculate similarity measures using various formulas as described in the previous sections (Fig. 1.36). 

When applying the AAA method the researcher must first decide what constitute the elements of the pharmacophore. Especially when the ligands have significantly different backbones or have many hydrocarbon regions, the question of which elements should be aligned can be difficult to answer 

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Dean P M (Editor) 1995. Molecular Similarity in Drug Design. London, Blackie Academic and Professional. 

C, E E Hodgkin and Richards W G 1993. The Utilisation of Gaussian Functions for the Rapid nation of Molecular Similarity. Journal of Chemical Information and Computer Science 32 188-192. C and I D Kuntz 1995, Investigating the Extension of Pairwise Distance Pharmacophore sures to Triplet-based Descriptors, Journal of Computer-Aided Molecular Design 9 373-379. 

Hodgkin E E and W G Richards 1987. Molecular Similarity Based on Electrostatic Potential and Electri Field. International Journal of Quantum Chemistry. Quantum Biology Symposia 14 105-110. 

J S, I Morize, P R Menard, D L Cheney, C Hulme and R F Labaudiniere 1999. New 4-Point irmacophore Method for Molecular Similarity and Diversity Applications Overview of the thod and Applications, Including a Novel Approach to the Design of Combinatorial iraries Containing Privileged Substructures. Journal of Medicinal Chemistry 42 3251-3264. 

Pearlman R S and K M Smith 1998. Novel Software Tools for Chemical Diversity. Perspectives in Dn Discovery and Design vols 9/10/ll(3D QSAR in Drug Design Ligand/Protein Interactions ar Molecular Similarity), pp. 339-353. 

There are now extensive databases of molecular structures and properties. There are some research efforts, such as drug design, in which it is desirable to hnd all molecules that are very similai to a molecule which has the desired property. Thus, there are now techniques for searching large databases of structures to hnd compounds with the highest molecular similarity. This results in hnding a collection of known structures that are most similar to a specihc compound. 

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... 

PC Model has some features that are not found in many other molecular mechanics programs. This is one of the few programs that outputs the energy given by the force field and the heat of formation and a strain energy. Atom types for describing transition structures in the MMX force field are included. There is a metal coordination option for setting up calculations with metal atoms. There are also molecular similarity and conformation search functions. 

P Willett. Algorithms for the calculation of similarity m chemical structure databases. In MA Johnson, GM Maggiora, eds. Concepts and Applications of Molecular Similarity. New York Wiley, 1990, pp 43-63. 

NC PeiTy, VI van Geerestem. Database searching on the basis of thi ee-dimensional molecular similarity using the SPERM program. I Chem Inf Comput Sci 32(6) 607, 1992. 

CHIRBASE Database Current Status and Derived Research Applications using Molecular Similarity, Decision Tree and 3D Enantiophore Search... 

Molecular similarity searching provides the possibility of finding unrelated but functionally analogous molecules. This is a very nice feature because many distinct structures in contact with a CSP often share the same active sites. The compounds which have a structure similar to the structure of the sample query can be displayed automatically in order of their similarity. The degree of similarity is measured by a numerical value on a scale of 0 to 100 that may be included in the output form. An example of a similarity search is shown in Fig. 4-3. In this example, a search is being performed for the AZT with a similarity value >65 %. 

Fig. 4-3. Molecular similarity searching of AZT in CHIRBASE. (Compounds reported in Refs. [7-12].)...

Dean, P. M. (ed.). Molecular similarity in Drug Design, Glasgow Blackie Academic and Professional, Chapman Hall, 1995. 

Bender A, Glen RC. Molecular similarity a key technique in molecular informatics. Org Biomol Chem 2004 2 3204-18. 

Lajiness MS. Molecular similarity-based methods for selecting compounds for screening. In Rouvray DH, editor, Computational chemical graph theory. New York Nova Science Publishers, 1990 299-316. 

Mason JS, Morize 1, Menard PR, Cheney DL, Hulme C, Labaudiniere RF. New 4-point pharmacophore method for molecular similarity and diversity applications Overview of the method and applications, including a novel approach to the design of combinatorial libraries containing privileged substructures. I Med Chem 1999 42 3251-64. 

In the original kNN method, an unknown object (molecule) is classified according to the majority of the class memberships of its K nearest neighbors in the training set (Fig. 13.4). The nearness is measured by an appropriate distance metric (a molecular similarity measure as applied to the classification of molecular structures). It is implemented simply as follows ... 

Johnson MA, Maggiora GM. Concepts and applications of molecular similarity. New York John Wiley Sons, 1990. 

Makara GM. Measuring molecular similarity and diversity total pharmacophore diversity. J Med Chem 2001 44 3563-71. 

Rarey M, Dixon JS. Feature trees a new molecular similarity measure based on tree matching. / Comput Aided Mol Des 1998 12 471-90. 

CoMSIA (comparative molecular similarity index analysis) is a recent development from CoMFA and does not suffer from the alignment problem. It has been used to model hERG potassium channel inhibition by drugs [59] and the toxicity of phenylsulfonyl carboxylates [60], organophosphates [61], and polybrominated diphenyl ethers [62], with results comparable to those from CoMFA. 

Molecular similarity has also been used directly to model toxicity. Bartlett et al. [63] found that the incidence of cutaneous rash from oral penicillins was a function of shape similarity to benzylpenicillin, and Basak et al. [64] used molecular similarity to model the mutagenicity of aromatic and heteroaromatic amines. 

Basak SC, Gute BD, Mills D, Hawkins DM. Quantitative molecular similarity methods in the property/toxicity estimation of chemicals a comparison of arbitrary versus tailored similarity spaces. J Mol Struct (Theochem) 2003 622 127-45. 

CoMSIA Comparative molecular similarity index analysis... 

Pan, D., Iyer, M., Liu, J., Li, Y., Hopfinger, A. J., Constructing optimum blood brain barrier QSAR models using a combination of 4D-molecular similarity measures and cluster analysis descriptors. J. Chem. Inf. Model. 2004, 44, 2083-2098. 

Raevsky, O. A., Dearden, J. C. Creation of predictive models of aquatic toxicity of environmental pollutants with different mechanisms of action on the basis of molecular similarity and HYBOT descriptors. SAR QSAR Environ. Res. 2004, 15, 433-448. 

Klebe, G., Abraham, U., Mietzner, T. Molecular similarity in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity./. Med. Chem. 1994, 37, 4130-4146. 

Allan NL, Du Z, Lavrentiev MY, Blundy JD, Purton JA (2003) Similarity in solid state chemistry trace element incorporation in ceramics minerals and melts. Proceedings of the Gerona Conference on Molecular Similarity (in press)... 

In more recent years, additional progress and new computational methodologies in macromolecular quantum chemistry have placed further emphasis on studies in transferability. Motivated by studies on molecular similarity [69-115] and electron density representations of molecular shapes [116-130], the transferability, adjustability, and additivity of local density fragments have been analyzed within the framework of an Additive Fuzzy Density Fragmentation (AFDF) approach [114, 131, 132], This AFDF approach, motivated by the early charge assignment approach of Mulliken [1, 2], is the basis of the first technique for the computation of ab initio quality electron densities of macromolecules such as proteins [133-141],... 

Carb6, R. (Ed.) (1995) Molecular Similarity and Reactivity From Quantum Chemical to Phenomenological Approaches, Kluwer Academic Publ., Dordrecht. 

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