Conformational analysis similarity measures

A similarity measure is required for quantitative comparison of one strucmre with another, and as such it must be defined before the analysis can commence. Structural similarity is often measured by a root-mean-square distance (RMSD) between two conformations. In Cartesian coordinates the RMS distance dy between confonnation i and conformation j of a given molecule is defined as the minimum of the functional... 

A similarity assessment of the shapes encoded by these vectors can be carried out on various levels. For two molecules (or conformers) Mj and M2, the number of matches along their C(M ) and C(M2) vectors, divided by the dimension (3 x 861), provides a simple, numerical similarity measure [262]. The comparison of the first 2 x 861 components [i.e., the comparison of vectors C( )(Mi) and C(2)(Mi) to C( )(M2) and C(2)(M2), respectively] appears the most important for a crude shape analysis, since these vectors store the information on the number and type of shape domains occurring for various a and b parameter values. By contrast, a direct comparison of vectors C<3)(M ) and C(3)(M2) gives information on the similarities of the patterns of different shape domains on the two families of molecular surfaces. 

PADRE ftp //ftp.CCL.net/pub/chemistry/ software/UNlX/PADRE/ Analysis of the results of conformational searches, and measurement of similarity and differences between molecules. 

It is noted that a similar approach carried out for polyethytene leads to an activation energy of 13.6 0.4 kJ/mol, for the relaxation of short (6-8 bonds) chain segments, regardless of the constraints imposed by chain connectivity [105]. This is in good agreement with the value 13.8kJ ol obtained by Brownian dynamics simulations of PE chains, and with NMR measurements of perfluoroalkane chains by Matsuo and Stodonayer, in which the mean orientational correlation times for C-F and C-H bends are found to have equal activation energies of about 12 kJ/mol. The barrier for internal rotation about typical CH2-CH2 bonds is slightly over 12 kJ/mol, from spectroscopic data and conformational analysis [3,106,107]. This value is exactly reproduced in the present theoretical treatment... 

Comparative Molecular Field Analysis (CoMFA) Conformational Flexibility in 3D Structure Searching Conformational Search Medium-sized Molecules Conformational Search Proteins Genetic and Evolutionary Algorithms Molecular Docking and Structure-based Design Shape Analysis Structural Similarity Measures for Database Searching Structure and Substructure Searching Structure Databases. 

Figure 2 Structural alignment methods with continuous properties. Methods are based on continuous properties using the algorithms implemented in MSA (I), HASL (II), and CoMFA (III). A conformational analysis (optional) can be used to select candidate conformations ( bioactive conformation, or alternatively a set of biologically relevant conformations that are used for the alignment). The structure representation is based on molecular shape (I), a four-dimensional lattice (II). or molecular fields (III). The different algorithms for the alignment require that a reference be cho.sen so that comparisons between each ligand and the reference can be made. A statistical measure of molecular similarity is performed to identify the alignment that maximizes the molecular similarity between the ligands in term.s of three-dimensional overlap (MSA, HASL) or electrostatic potential distributions...

A cluster analysis requires a measure of the similarity (or dissimilarity) between pairs of objects. When comparing conformations, the RMSD would be an obviou.s measure to use. 

For compounds that conform to the mechanism of scheme C, an alternative method for defining inhibition modality is to measure progress curves (or preincubation effects vide supra) at varying inhibitor and substrate concentrations, and to then construct a double reciprocal plot of 1/v, as a function of l/[.Sj. Using the analysis methods and equations described in Chapter 3, one can then determine the modality of inhibition for the inhibitor encounter complex. Similarly, for inhibitors that conform to the mechanism of scheme B, a double reciprocal plot analysis of l/vs as a function of 1/[S] can be used to define inhibition modality. 

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