Molecular structures superimposition

Figure 14.12. Superimposition of molecular structures with HyperChem. Pigeon lysozyme structure (red) derived from homology modeling with Swiss-PDB Viewer is overlapped against chicken lysozyme structure, pdb1 lyz.ent (black). Two catalytic residues, Glu35 and Asp 52 (chicken lysozyme), are highlighted (green).

In contrast to topological approaches, methods based on geometrical representations of molecular structures can be used instead. Among them, flexible superimposition of molecules onto one or multiple conformations of a reference bioactive ligand is a well-established methodology... 

Generally, the most abundant DDT-metabolites released by the degradation procedures used were 4,4 -DBP, 4,4 -DDA and 4,4 -DDM. The altered distribution of bound DDT-related compounds indicates either (i) a different biotic or abiotic degradation pathway of bound DDT and/or its main metabolite (DDD), or (ii) a selective association of individual metabolites due to their different molecular structures and physicochemical properties without further alteration of the incorporated substances. Also a superimposition of both environmental fates suggested is conceivable, e.g., the association of selected metabolites followed by a modified transformation pathway as compared to the non-bound compounds. 

FIGURE 71 Optimized superimposition of the molecular structures of [EuLaEu(L28)3] and [Eu3(L28)3] viewed perpendicular to the pseudo-Ci-ax s (adapted from Floquet et al 2004). 

The structure of the molecular supergraph is shown in Figure 5.9 with several examples of superimposition of the training set structures. It reflects substantial diversity of the training set compounds and, despite apparent complexity, supports reasonable comparison of different structures. Simpler MSGs could... 

First-order connectivity indices computed for predefined positions on molecular fragments in congeneric series [Takahashi et al, 1985]. By superimposition of all congeneric compounds, a template structure is derived whose vertices define the positions for the FMC indices the vertices of the common parent structure are not considered in defining the positions. For a k th position the corresponding fragment connectivity index is defined as ... 

The nature of the association process (inter- or intramolecular) can be revealed by mixing compounds of the same structure but different molecular mass [34, 37]. Because the mobility of the investigated compounds is mass-dependent, with intramolecular association the electropherogram of the mixture should indicate superimposition of the two single injection peaks. If intermolecular associates are predominantly formed, one single, sharp peak should appear for the mixture. Both cases could be realized in practice ... 

Molecular Manipulation and Superimposition. To facilitate molecular comparisons, a variety of computer graphic techniques are available for three-dimensional manipulation and display of the stored structures in the library file (12,13). In our laboratory lateral stereo pair views of either single line or ball and stick models are displayed on a Tektronix 4014 graphics terminal linked to a Univac 1100/42 computer. 

However, a unique enumeration does not solve the problem of substructure search. Superimposition of substructures on structures would require the mapping of any combination of molecular graphs to find a graph isomorphism this is a tedious and time-consuming process. Because the rate of search is always one of the most important limitations for database applications, substructure search should incorporate additional preprocessing steps that restrict the number of molecules to be compared in an atom-by-atom matching algorithm. 

Besides the statistical prediction of biological activity based on the rules, the deductive inference module provides explanation of predictions. It produces a three-dimensional graphic display of biophores found in the analyzed structures and allows superimposition of compounds with the same biophore. Visualization is performed via integration with the Insight II environment from Accekys Inc. [21], a molecular modeling environment with a powerful graphical interface. 

Structure alignment The superimposition or fitting of the 3-D structures of molecules can be based on electron density, atom positions, molecular electrostatic fields, or secondary structures. This is a crucial step for 3D-QSAR and x-ray structure elucidation. 

In enzymic reactions as well as in catalysis, the substituents affect the energy of reacting intra-index bonds because of the displacement of electrons. A finer tuning gives the structural correspondence of the substituents. The heterogeneous catalysis of optically active substances points to it (see Section I,F). The superimposition of extra-index substituents on the carrier near the active center is because of molecular adsorption or the H bonds. 

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