Local shape groups

Shape Similarity Measures of Functional Groups Based on Local Shapes... 

Local Shape Complementarity Measures for Functional Groups... 

An important concern is the efficient detection of local shape changes introduced by chemical changes in remote locations of a molecule. One simple approach [20] applied a truncation method, compatible with the truncation process already used within the shape group methods for molecular shape analysis [41-44]. 

Skinny molecular range, [af, a< ) af is defined above, whereas is the maximum threshold at and below which all locally nonconvex domains on the surface of density domains are simply connected. In simpler terms, in the skinny molecular range all nuclei are found within a single density domain, but there are formal "neck regions on the surface of density domains. In the terminology of shape group analysis [2], rings of D) type can be found on the surface of density domains. 

The reactivities of functional groups are highly dependent on the molecular surroundings, and the effects of the global molecular environment on the local shape variations can be significant. 

The fundamental principle we shall follow in the local shape analysis of functional groups and local molecular moieties is a strict analogy with the shape analysis of complete molecules. Accordingly, instead of molecular isodensity contour (MIDCO) surfaces, the main tool of analysis will be the fragment isodensity contour (FIDCO) surfaces. Some of the ideas and concepts described in this section are illustrated in Figure 1. 

Two choices for the representation of a local molecular moiety will be discussed. For the first choice, describing the local shapes of non-interacting functional groups within a molecule, we define a FIDCO for a fragment A in a molecule AB as follows ... 

Figure 1. Illustration of the local shape description of non-interacting and interacting functional groups. See text for definitions of symbols.

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. 

In general, a locally convex domain D2(b),j(a> Fj) of a functional group F, relative to a reference curvature b, shows local shape complementarity with a locally concave domain Do( b),j(a, F2) of a complementing functional group F2, relative to a reference curvature of -b. The threshold values a and a are also likely to complement each other the shape complementarity between the higher electron density contours of one functional group and the lower electron density contours of the other functional group is relevant. 

If a contact density threshold ao can be chosen for a given interaction between two functional groups, then the local shape complementarity between G(ao, Fj) and G(a<), F2) is clearly of importance. However, complementarity should also manifest itself within a whole range of density thresholds. One may consider the local shape complementarity of FIDCOs G(ao-a, F[) and G(ao+a, F2) in a density interval containing the contact density threshold ao,... 

For example, if the shape domains are defined in terms of local convexity, and if we select the locally convex domains, then the shape groups of G(a) are the homology groups of the truncated isodensity contour surface G(a,2), obtained from the molecular contour surface G(a) by eliminating all domains of index p = 2. This family of shape groups, obtained by cutting out all locally convex domains of G(a), has been studied in most detail for several molecules [192,262,263,342]. 

If the shape domains are defined by relative local convexity, then the notation HP j (a,b), p = 0, 1,2, is u.sed for the shape groups of MIDCO surfaces G(a), where besides the dimension p of the homology group, the truncation type p, the charge density contour parameter a, and the reference curvature parameter b are also specified. For the special case of ordinary local convexity, b=0, the second argument in the parentheses can be omitted and one may simply write HP (a). Usually, we are interested in the Betti numbers of the groups HP (a,b) and HP (a) for these numbers the bp x(a,b) and bpp(a) notations are used, respectively. 

The nondifferentiability of these surfaces at the seams of interpenetrating spheres as well as the local nondifferentiability of solvent accessible surfaces or union surfaces, are a technical disadvantage. Local nondifferentiability limits the application of the shape group methods in their original form that requires second derivatives for curvature analysis. For example, at every point r of a VDWS where two or more atomic spheres interpenetrate one another, the surface is not smooth and is not differentiable. For such nondifferentiable molecular surfaces, alternative shape descriptors and shape codes have been introduced. 

In many chemical problems the comparisons of local molecular regions are more important than global comparisons. The presence of functional groups or other molecular moieties with specified shape properties often imply similar chemical behavior even if the molecules compared have very different global shapes. For this reason, local molecular shape descriptors and local shape codes are of major importance. 

For most practical applications, CIMM is used within the framework of local measures. These measures are based on local shape matrices or on the shape groups of local moieties, defined either by the density domain approach mentioned earlier, or by alternative conditions, such as the simple truncation condition replacing the "remainder" of the molecule by a generic domain [192], For proper complementarity, identity or close similarity of the patterns of the matched domains is an advantage, hence the parts Cl HM)) and Cl KM2) of the corresponding local shape codes are compared directly. For shape complementarity only the specified density range [bq - Aa, Bq + Aa] and a specified curvature range of the (a,b) parameter maps is considered. A local shape complementarity measure, denoted by... 

Shape codes [43,109,196,351,408]. The simplest topological shape codes derived from the shape group approach are the (a,b) parameter maps, where a is the isodensity contour value and b is a reference curvature against which the molecular contour surface is compared. Alternative shape codes and local shape codes are derived from shape matrices and the Density Domain Approach to functional groups [262], as well as from Shape Globe Invariance Maps (SGIM). 

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