Weighted representations, molecular similarity

Todeschini, R., Consonni, V., Galvagni, D. and Gramatica, P. (1999). A New Molecular Structure Representation Spectral Weighted Molecular (SWM) Signals for Studies of Molecular Similarity. Quimica Analitica, 18, 41-47. 

Aligned differences may also come into play in molecular similarity for representations based on weighted molecular fingerprints, hi this case, the count of (typically substructural) features may differ between two molecules for particular features such... 

In actual applications of MSA, many different types of representations are utilized to compute molecular similarities [41, 52-54]. Johnson [55] has provided a detailed discussion of the manifold types of mathematical spaces and their associated representations. The information contained in the representations is usually in the form of molecular or chemical features called descriptors that are derived from the structural and chemical properties of molecules. Descriptors ate nominally classified as ID (one-dimensional), 2D, or 3D. ID descriptors are usually associated with whole molecule properties such as molecular weight, logP, solubility, number of hydrogen bond donors, nnmber of rotatable bonds, and so on. 2D descriptors are associated with the topological strnctnre of molecules as typically depicted in chemists drawings. Such depictions show the atoms, the bonds connecting them, and in some cases include stereochemical features, but they do not explicitly depict the 3D structures of molecules. 3D descriptors, as their name implies, are associated with the 3D structures of molecules. Todeschini and Consonni [56] have compiled an extensive reference containing many of the descriptors used in chemical informatics applications. 

Solutions of high-molecular-weight polymers exhibit similar temperature dependence, but the coefficient Bt cannot be predicted from thermodynamic properties. It depends on the structural and thermal properties of the polymer. Data are analyzed in terms of mathematical representations of viscosity in which appropriate coefficients are related to structural considerations. 

Thorner, D.A., Willett, P., Weight, P.M., and Taylor, R. Similarity searching in files of three-dimensional chemical structures Representation and searching of molecular electrostatic potentials using field-graphs./. Comput.-Aided Mol. Des. 1997, 3 3, 163-174. 

Standardized and consistent representations of stereoisomers and stereoisomeric mixtures are similarly important for the unique representations of distinct compounds. Recent file formats such as SDF v3000 and ChemAxon Extended SMILES provide clear definition and representation of complex relative and absolute stereochemical configurations. In practice these are not widely used because many commercially available files are represented by established v2000 or SMILES formats and also because HTS compounds are mostly relatively simple low molecular weight structures. 

Figure 4. Linear representation of the Arabidopsis PIPKs and PLCs. The Arabidopsis PtdlnsP 5-kinases are most similar to the human type I PtdlnsP 5-kinases. There are 11 putative type I /I/PtdlnsP 5-kinases in Arabidopsis arranged in two subfamilies based on size. Subfamily B contains X/PIPK1-9, all of which contain membrane occupation and recognition nexus (MORN) repeats. /1/PIPK10-11 are in Subfamily A with molecular weights less than that of the members of subfamily B and contain no MORN repeats. The Arabidopsis phosphoinositide specific phospholipase C family is most similar to the animal PLC . There are seven functional PI-PLCs in Arabidopisis (Hunt et al., 2004). All isoforms contain EF-hand motifs, the X and Y catalytic domains characteristic of PI-PLCs and a C2 lipid-binding domain.

Statistical copolymers of uBA and IBA with different molecular weights and compositions were synthesized under ATRP conditions, as described in detail earlier (26). In all ATRP reactions, a CuBr/PMDETA complex was used since it is commercially available and well mediates controlled polymerization of acrylate monomers. Polymerizations were performed at 50°C in acetone/anisole mixture using EtBrIB as the initiator. The schematic representation of all prepared materials is shown in Scheme 2. The solid line represents a series of polymers with similar DP but systematically increasing IBA content. Another such group of copolymers is indicated with a dashed line. Copolymers with similar IBA/nBA ratio but different degree of polymerization (DP), i.e., the dotted line, were also synthesized. When comparing the thermo-mechanical properties of acrylate homopolymers and P(IBA-co-nBA) copolymers, the first important question is whether the copolymer system is isotropic in the bulk state or rather exhibits a micro-phase separation. To answer this question, the DSC thermograms for all samples shown in Scheme 2 were measured. 

Section 15.4 provides a discussion of similarity measures, which depend on three factors (1) the representation used to encode the desired molecular and chemical information, (2) whether and how much information is weighted, and (3) the similarity function (sometimes called the similarity coefficient) that maps the set of ordered pairs of representations onto the unit interval of the real line. Each of these factors is discussed in separate subsections. Section 15.5 presents a discussion of a number of questions that address significant issues associated with MSA Does asymmetric similarity have a role to play Do two-dimensional (2D) similarity methods perform better than three-dimensional (3D) methods Do data fusion and consensus similarity methods exhibit improved results Are different similarity measures statistically independent How do we compare similarity methods Can similarity measures be validated S ection 15.6 provides a discussion of activity landscapes... 

Hence, stmctural information can be lost leading to similarity values of unity for pairs of molecules that are not stracturally identical. Nevertheless, there is at least a partial correspondence between the descriptors in the directory and the binary molecular FP of a molecule, so that it may be possible in many instances to associate particular substmctural features with molecular properties and/or biological activities, a characteristic that is not generally shared by molecule-dependent FP representations vide infra). This can be partially ameliorated through the use of weighted molecular FPs that take account of the nmnber of times a stractural feature occurs in a molecule. However, since not all structural features that may be associated with a specific structure-property relationship (SPR) or stmcture-activity relationship (S AR) are necessarily accounted for in given FP, it may not be possible to infer SPR or SAR even when weighted FPs are employed. 

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