Atom-type definitions

The most well-known and at the same time the earliest computer model for a molecular structure representation is a wire frame model (Figure 2-123a). This model is also known under other names such as line model or Drciding model [199]. It shows the individual bonds and the angles formed between these bonds. The bonds of a molecule are represented by colored vector lines and the color is derived from the atom type definition. This simple method does not display atoms, but atom positions can be derived from the end and branching points of the wire frame model. In addition, the bond orders between two atoms can be expressed by the number of lines. 

Table 10.1 Atom-type definitions used in deriving EnTess.

Besides differences in the functional form and reference state, from a more practical point of view, the knowledge-based potentials differ also with respect to scope of atom type definitions and the amount of structural data used for their derivation. The number of different atom types ranges from 17 in Drug-Score to 40 nonmetal atom types in BLEEP. In all cases, the Protein Data Bank (321) was the source of the solved crystal structures. For BEEEP 351 selected complexes were used, whereas the PMF function was extracted from 697 complexes, and DrugScore was derived using 1376 complexes. In the latter case, the data have been extracted from Relibase (322,323). 

Two other atomic properties have been used in the definition of atom type, thereby increasing its fuzziness relative to that in the ap and tt descriptors - atomic log P contribution (yielding hydrophobic pairs, hps, and torsions, hts) and partial atomic charges (charge pairs, cps, and charge torsions, cts). 

Atom types represen t the chemical environment of an atom. The atom types associated with a given force field could be hard-wired to have specific vahiesand meaning. llyperChem also allows flexible definitions of the atom types and the associated chemical en vironmen Is. Th e ch em ical en viron men t of an atom (a set of rules for defining a type) and the default rules are in a standard ASCII text file, chem.nil. included with llyperChem. You can modify this file and compile it m a binary form that llyperChem... 

Leatherface allows definition of atom types that can be used to specify more complex SMARTS patterns. This is done in a separate input file and can lead to a more readable specification of substructure. Neutral aliphatic amines can be defined as follows ... 

A SMARTS definition can be buHt using this atom type to direct structural editing. 

Our current ionization and tautomer model encodes biased and balanced equilibria with 108 and 35 rules respectively. Extensive use is made of atom typing to specify chemistry in as generic a manner as possible, which reduces the number of rules required, for example, a number of heteroaromatic nitrogen types, including selected 2-aminopyridines and imidazoles, are aggregated into a definition of bases with pK ... 

These methods were developed to avoid the definition and parameterization of numerous fragments or atomic types and to allow the prediction of lipophilicity for stereoisomers or conformers. Only a selection of methods are highlighted here, since an excellent extensive review was recently published [34]. 

The first general parameterization to be reported by Dewar and co-workers was a third-generation modified INDO model (MINDO/3 Bingham, Dewar, and Lo, 1975). Some of the specific modifications to the INDO framework included the use of different t exponents in s and p type STOs on the same atom, the definition of pair parameters /Iab between two atoms A and B that were not averages of atomic parameters (actually, four such parameters... 

Fig. 3.4 Definition of scaffold (Sc) and reduced scaffold (ReSc). In this work we defined the scaffold of a molecules as the side-chain depleted molecular graph without annotation of atom types. A reduced scaf-...

The latter scenario is sometimes referred to as scaffold or lead hopping [22-25]. This is a formidable challenge for the descriptor and the similarity measure. While avoiding the chemical graph and atom type-based molecular representation, the essential features required for activity have to be retained. By definition, such a task will be prone to picking out false positives and, therefore, requires a fast search in large and diverse databases together with a tunable level of similarity. 

In Table 6.8, atom type-specific subset correlations of AMI, PM3, PM5, and HF with B3LYP are shown for frontier orbital energies and related descriptors, for parameters based on the charge distribution, and for the PPSA and PNSA descriptors. In contrast to Table 6.4 and Table 6.7, however, now all compounds providing a zero descriptor value by definition (e.g., PPSA-1Z = 0 if, for a given method, the compound has no positively charged heavy atom) were included for generating the statistics. 

A powerful extension to the potential pharmacophore method has been developed, in which one of the points is forced to contain a special pharmacophore feature, as illustrated in figure 4. All the potential pharmacophores in the pharmacophore key must contain this feature, thus making it possible to reference the pharmacophoric shapes of the molecule relative to the special feature. This gives an internally referenced or relative measure of molecular similarity/diversity. The special feature can be assigned to any atom-type or site-point, or to special dummy atoms, such as those added as centroids of privileged substructures [7, 10]. With one of the points being reserved for this special feature, it would seem even more necessary to use the 4-point definition to capture enough of the... 

Atoms and even the PO4 unit in a phosphate crystal may be considered as spherical balls and stacked in various configurations. The PO4 unit is held together in solids by five types of bonds. These bonds, which hold the atoms at definite distances from each other, are formed by the electronic configuration of the atoms. The equilibrium distance between... 

The present description will utilize cartesian coordinates = rj,r2,..., r where the Vj locates the / atom taken as distinguishable but with definite, assigned atom-type. We assume that U X") is unchanged when atoms of the same type exchange locations. 

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