Comparative molecular surface

Polanski J, Gieleciak R, Bak A (2002) The comparative molecular surface analysis (COMSA) - a nongrid 3D QSAR method by a coupled neural network and PLS system Predicting pKa values for benzoic and alkanoic acids. J Chem Inf Comput Sci 42 184-191... 

In situations where, either from previous QSAR work or from experimental evidence, it is known or suspected that differences in the reactivity of a set of molecules are attributed primarily to their hydrophobic rather than their electrostatic properties it is probably of more use to compare molecular surfaces that display hydrophobicity or polarity information. Indeed, dotted molecular surfaces color-coded by hydrophobic character have been used very successfully by Hansch and coworkers to rationalize QSARs from several different systems (418,419). This concept has been extended to calculate the hydrophobic field surrounding a molecule by Kellogg and Abraham (420,421 )and utilized in CoMFA studies. 

Comparative Molecular Similarity Indices Analysis grid-based QSAR techniques > Comparative Molecular Surface Analysis grid-based QSAR techniques > Comparative Receptor Surface Analysis = CoRSA > Comparative Spectral Analysis spectra descriptors... 

COMSA = Comparative Molecular Surface Analysis topological feature maps... 

The most popular grid-based QSAR techniques are GRID and CoMPA, based on molecular interaction fields derived from different probes these methods together with a number of related techniques are discussed below other related techniques are —> hydration free energy density and —> Comparative Molecular Surface Aitalysis. 

Self-organizing map for describing chemical information of a molecule is also used in —> Comparative Molecular Surface Analysis and topological feature maps. 

Several QSAR approaches are based on Kohonen maps, such as topological feature maps. Comparative Molecular Surface Analysis, and MOLMAP descriptors. Counter-propagation neural network is a development of Kohonen maps for classification purposes [Zupan, Novic et al., 1995], which considers a set of output layers, called Grosberg... 

The Comparative Molecular Surface Analysis (CoMSA) is a 3D-QSAR approach that makes use of the topological feature maps combined with PLS method to quantitatively predict... 

Hasegawa, K., Morikami, K., Shiratori, Y, Ohtsuka, T, Aoki, Y. and Shimma, N. (2003) 3D-QSAR study of antifungal N-myristoyltransferase inhibitors by comparative molecular surface analysis. Chemom. Intell. Lab. Syst., 69, 51—59. 

Polanski, J. and Gieleciak, R. (2003) The comparative molecular surface analysis (CoMSA) withmodified uniformative variable elimination-PLS (UVE-PLS) method application to the steroids binding the aromatase enzyme. J. Chem. Inf. Comput. Sci., 43, 656—666. 

Polanski, J. and Walczak, B. (2000) The comparative molecular surface analysis (COMSA) a novel tool for molecular design. Computers Chem., 24, 615-625. 

Further additions to the 3D-QSAR arsenal include comparative molecular similarity indices analysis (CoMSIA) [15], 4D-QSAR [16], COMPASS [17], receptor surface models [18], the pseudoreceptor approach [19], ComPharm [20], and comparative molecular surface analysis (CoMSA) [21], 3-D-invariant, alignment-free descriptor systems such as comparative molecular moment analysis (CoMMA) [22], EVA [23], WHIM [24], and ALMOND [25], have also become available. A survey of the 3D-QSAR literature reveals 1154 entries in the Chemical Abstracts Plus database of these, 79% are journal publications, 19% are conference proceedings, and four are patents related to, or using, 3D-QSAR models. As the number of potential targets amenable to drug discovery is increasing exponentially, it is likely that 3D-QSAR models and methodologies will continue to be developed in the next decade. 

USE 3D QSAR study of hypolipidemic asarones by comparative molecular surface analysis [7519]. 

The Surflex-Sim method operates significantly differently [104]. Each of the molecules is surrounded by a set of observer points that characterizes the local character of the surface and potential interactions. Two similar molecules will have a common subset of comparable observer points. A optimal alignment occurs when the differences in pharmacophore character and molecular surface inferred from the observer points are minimized between two molecules. To speed up the algorithm, large molecules can be fragmented into parts which are then compared, and then tested for consistency. This feature also makes the method capable of identifying alignments when one molecule is much smaller than the other. 

In their study of branched PSA, Maniar et al. (1990) found that the molecular architecture of branched polymers affects the release kinetics in a variety of ways. They found that the branched polymers degraded faster than linear PSA of comparable molecular weight (Maniar et al., 1990). They also noted that drug (morphine) release profiles were more characteristic of bulk erosion than surface erosion An initial lag time during which very little drug was released was associated with the time required for water to swell the polymer. This was followed by a period of relatively fast release, which tapered off as the device disintegrated. The polymer matrix lost its mechanical integrity before the release experiment was complete (Maniar et al., 1990). Despite the increase... 

On the other hand, there is considerable interest to quantify the similarities between different molecules, in particular, in pharmacology [7], For instance, the search for a new drug may include a comparative analysis of an active molecule with a large molecular library by using combinatorial chemistry. A computational comparison based on the similarity of empirical data (structural parameters, molecular surfaces, thermodynamical data, etc.) is often used as a prescreening. Because the DFT reactivity descriptors measure intrinsic properties of a molecular moiety, they are in fact chemical fingerprints of molecules. These descriptors establish a useful scale of similarity between the members of a large molecular family (see in particular Chapter 15) [18-21],... 

Dendrimer synthesis involves a repetitive building of generations through alternating chemistry steps which approximately double the mass and surface functionality with every generation as discussed earlier [1-4, 18], Random (statistical) hyperbranched polymer synthesis involves the self-condensation of multifunctional monomers, usually in a one-pot single series of covalent formation events [31], Random hyperbranched polymers and dendrimers of comparable molecular mass have the same number of branch points and terminal units, and any application requiring only these two characteristics could be satisfied by either architectural type. Since dendrimer synthesis requires many defined synthetic and process purification steps while hyperbranched synthesis may involve a one-pot synthetic step with no purification, the dendrimers will necessarily be a much more expensive material to produce. 

Ekins et al. (163) used the rat ortholog 2B6 to generate a pharmacophore model and compared these findings with a partial least squares (PLS) model using MS-WHIM descriptors. The model was constructed using 16 B-lymphoblastoids and yielded a good cross-validated r2 of 0.607. The analysis included molecular surface properties (size) together with positive elec-... 

MS-WHIM, new 3D theoretical descriptors derived from molecular surface properties a comparative 3D QSAR study in a series of steroids../. Comput. 

If complete adsorptive molecular layers inhibit further dissolution of silicic acid, all experimental phenomena are explicable. In this case the final experimental concentration is not a saturation concentration which can be obtained also from high initial concentrations of silicic acid. Instead, the concentration will decrease only to the extent that the adsorption equilibrium is established. For sufficiently high initial concentrations of silicic acid and comparatively small surface areas, this will involve a multimolecular layer, whose equilibrium concentration is higher than the final experimental concentration of the self-inhibiting dissolution process. 

A quite different approach to the molecular size of solvents is the estimation of its molecular surface area and volume from the van der Waals radii of the constituent atoms and the manner and geometry of their mutual bonding (Bondi 1964). The necessary calculations are quite involved, and the values shown in Table 3.4 have been taken from a single source (DIPPR 1997), in order to be consistent. The reported molar van der Waals surface areas, Ayiw, are in 104 m2 mol 1 and the molar van der Waals volumes, Fvdw, are in cm3 mol 1, the latter in order to be comparable with the molar volumes (in Table 3.1) and the intrinsic volumes, defined below, also reported in Table 3.4. 

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