Special atoms, types

Note that special atom types are defined for carbon atoms involved in small rings, like cyclopropane and cyclobutane. The reason for this will be discussed in Section 2.2.2. 

The MM2 force field3 is probably the most extensively parameterized and intensively used force field to date. It reproduces a variety of molecular properties such as geometry, dipole moments, conformational energies, barriers to rotation and heats of formation. Of particular importance for calculations of amines is that MM2 treats lone pairs on sp3 nitrogens (and oxygens) as pseudo atoms with a special atom type and parameters. A closely related force field, MM2 7, was derived from MM2 by Osawa and Jaime. MM2 uses the same potential functions as MM2, but employs a different set of parameters in an attempt to better reproduce barriers to rotation about single C—C bonds. 

A central issue is the number of different atom types that are used in a particular force field. There is always a compromise between increasing the number to allow for the inclusion of more environmental effects (i.e., local electronic interactions) vs. the increase in the number of parameters to be determined to adequately represent a new atom type. In general, the more subtypes of atoms (how many different kinds of nitrogen, for example), the less likely that the parameters for a particular application will be available in the force field. The extreme, of course, would be a special atom type for each kind of atomic environment in which the parameters were chosen, so that the calculated properties of each molecule would simply reproduce the experimental observations. One major assumption, therefore, is that the force constants (parameters) and equilibrium values of the equations are functions of a limited number of atom types and can be transferred from one molecular environment to another. This assumption holds reasonably well where one may be primarily interested in geometric issues, but is not so valid in molecular spectroscopy. This had led to the introduction of additional equations, the so-called "cross-terms" which allow additional parameters to account for correlations between bond lengths and bond angles... 

As noted above, special atom types are often defined for small rings. This is due to the... 

Since in the decision tree related structures are located in non-distant parts of the tree, the system is well suited to the simultaneous retrieval of a set of similar structures, therefore the HTSS system is able to retrieve very complex Markush queries with good response times. A biographical multiwindow technique has been implemented in the user interface of the HTSS system to enable the easy entry of Markush queries. Functional groups can be defined by the user as special atom types. 

Usually the constants involved in these cross terms are not taken to depend on all the atom types involved in the sequence. For example the stretch/bend constant in principle depends on all three atoms. A, B and C. However, it is usually taken to depend only on the central atom, i.e. = k , or chosen as a universal constant independent of atom type. It should be noted that cross tenns of the above type are inherently unstable if the geometry is far from equilibrium. Stretching a bond to infinity, for example, will make str/bend go towards — oo if 0 is less than If the bond stretch energy itself is harmonic (or quartic) this is not a problem as it approaches +oo faster, however, if a Morse type potential is used, special precautions will have to be made to avoid long bonds in geometry optimizations and simulations. 

Special structural types of selected metals. In this paragraph a few selected special structures peculiar to some metals, generally located in particular positions of the periodic table, are described. Some very simple structural types have to be considered (the simplest one is the aPo-cPl) and some having rather complex atomic arrangements, for instance otMn, cI58. 

For each of the three Estretch(X-Y) terms, kstretch(X-Y) and leq(X-Y) are needed, for a total of 6 parameters. For each of the three Ebend(XYZ) terms, kbend(XYZ) and aeq(XYZ) are needed, for a total of 6 parameters. The torsional curve likely requires at least 5 parameters (see chapter 3, section 3.2.2) for reasonable accuracy. This makes a total of 6 + 6 + 5 = 17 parameters. But this would be a very stunted forcefield it has no parameters for nonbonded interactions and so is not suitable for molecules with bulky groups, and it is parameterized only for the atom types sp3 C, H, and Cl. It cannot handle other kinds of carbon and other elements, and it has no special parameters for electrostatic interactions. 

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... 

For site-points, one of the points just needs to be manually reassigned to an otherwise unused atom type, to which the special feature is assigned. Figure 6 illustrates relative pharmacophores in a site context. 

Atom and bond matrices can be used for calculation. A special form of a connection table is the adjacency matrix, which contains information about the connections between atoms without atom types and bond order. The adjacency matrix, M, of a chemical structure is defined by the elements, M-, where is 1 if atoms i and j are... 

Moreover, a special case of autocorrelation descriptors is the Atom-Type Autocorrelation (ATAC), which is calculated by summing property values only of atoms of given types. The simplest atom-type autocorrelation is given by... 

Atom types can be defined in different ways they can be defined in terms of the simple chemical elements or may account also for atom coimectivity, hybridization states, and pharmacophoric features. Atom-type autocorrelations can be viewed as a special case of the —> atom-type interaction matrices, from which other kinds of descriptors can also be derived. 

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