Molecular shape-complementarity

This generalization of the Centrally Inverted Map Method (CIMM) of molecular shape complementarity analysis [2] to FIDCOs of functional groups replaces the problem of complementarity evaluation with a conceptually and computationally simpler similarity evaluation. 

Molecular shape complementarity is critical to biomolecular recognition and specificity. Even if the molecules change conformation on binding and water molecules are trapped at the interface, bound complexes show high shape complementarity (31). This shape complementarity is dependent on van der Waals interactions between the binding molecules. Electron-electron repulsion prevents atomic overlap and intermolecular penetration. However, induced dipole effects as atoms approach lead to short-range attractive interactions. 

This Centrally Inverted Map Method (CIMM) of molecular shape complementarity analysis allows one to use the techniques of similarity measures. In fact, the problem of shape complementarity is converted into a problem of similarity between the original (a,b) parameter map of shape groups HP (a,b) of molecule M] and the centrally inverted (a,b) parameter map of the complementary HP2-ii(a,b) shape groups of molecule M2. 

The spherically shaped cryptophanes are of much interest in particular for their ability to bind derivatives of methane, achieving for instance chiral discrimination of CHFClBr they allow the study of recognition between neutral receptors and substrates, namely the effect of molecular shape and volume complementarity on selectivity [4.39]. The efficient protection of included molecules by the carcerands [4.40] makes possible the generation of highly reactive species such as cyclobutadiene [4.41a] or orthoquinones [4.41b] inside the cavity. Numerous container molecules [A.38] capable of including a variety of guests have been described. A few representative examples of these various types of compounds are shown in structures 59 (cyclophane) 60 (cubic azacyclophane [4.34]), 61a, 61b ([4]- and [6]-calixa-renes), 62 (cavitand), 63 (cryptophane), 64 (carcerand). 

Precise molecular shape is of crucial importance to every living organism. Almost every chemical interaction in living systems is governed by complementarity between handed molecules and their glovelike receptors. 

This approach depends on the process of molecular recognition, which is based on the complementarity of the molecular shapes of the host and guest, and is shown schematically in Figure 1. 

Figure 12 Conformation of statherin on HAp surface determined by molecular modelling. The four basic residues (K6, R9, RIO, and R13) fit nicely to the IPOT motif (outlined in dots). FADE scores are quantitative measure of shape complementarity. (Reprinted with permission from Ref. 181. 2007 American Chemical Society.)...

Gabb HA, Jackson RM, Sternberg MJE (1997) Modelling protein docking using shape complementarity, electrostatics and biochemical information. J Molecular Biology 272(1) 106—120... 

Shape Similarity and Shape Complementarity Measures of Functional Groups in Different Molecular Environments... 

SHAPE SIMILARITY AND SHAPE COMPLEMENTARITY MEASURES OF FUNCTIONAL GROUPS IN DIFFERENT MOLECULAR ENVIRONMENTS... 

In most interactions between two reactants, local shape complementarity of functional groups is of importance. A local shape complementarity of molecular electron densities represented by FIDCOs implies complementary curvatures for complementary values of the charge density threshold parameters a. For various curvature domains of a FIDCO, we shall use the notations originally proposed for complete molecues [2], For example, the symbol D2(b),i(a, Fj) stands for the i-th locally convex domain of a FIDCO G(a) of functional group Fj, where local convexity, denoted by subscript 2(b), is interpreted relative to a reference curvature b. For locally saddle type and locally concave domains relative to curvature b, the analogous subscripts 1(b) and 0(b) are used, respectively. 

We have presented a netv procedure, called PathFinder, aimed at encoding the GRID molecular interaction fields into invariant shape-descriptors, suitable for similarity and complementarity issues. Shape similarity is the underlying foundation of ligand-based methods tvhile shape complementarity is the basis of many receptor-based designs. 

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