Three-dimensional chemical representation

Clark DE, Willett P, Kenny PW. Pharmacophoric pattern matching in files of three-dimensional chemical structures use of smoothed bounded-distance matrices for the representation and searching of conformationally-fiexible molecules. J Mol Graph 1992 10 194-204. 

Thorner, D.A., Willett, P., Weight, P.M., and Taylor, R. Similarity searching in files of three-dimensional chemical structures Representation and searching of molecular electrostatic potentials using field-graphs./. Comput.-Aided Mol. Des. 1997, 3 3, 163-174. 

Drawing the structure of a chemical compound is probably one of the first basic requirements of any chemist. It requires knowledge of the chemical composition of the structure to be drawn, an understanding of the type of bonding, and frequently a mental visualization of the arrangement of atoms (or ions). Once this has been assimilated it is not uncommon to draw a representation of the structure on paper. What is often lacking is the realization that the molecule should be represented in three dimensions. To some extent it is possible to represent a three-dimensional chemical structure on a piece of paper. Fig. 42.1 shows the structure of methane, CH4, where standard symbols e.g. the hatched hne, are used to imply a direction of the bond, and one that is different to, for example, the solid hne. This simple notation is commonly used to give a molecule the perception of three-dimensionality. 

Clark, D.E., Willett, P. and Kenny, P. (1992). Pharmacophoric Pattern Matching in Files of Three-Dimensional Chemical Structures Use of Smoothed-Bounded Distance Matrices for the Representation and Searching of Conformationally-Flexible Molecules. J.MoLGraphics, 10,194-204. 

Figure 1.10. (a) Chemical structure of p-C P,. (b) Two-dimensional (2D) representation of where chromophores can be attached to the dendrimer and (c) three-dimensional (3D) representation of isomer 2A2B of p-C1P2. The arrows indicate the possible substitution patterns. 

D. A. Thorneg P. Willett, P. M. Wright, and R. Taylor, J. Comput.-Aided Mol. Des., 11,163 (1997). Similarity Searching in Files of Three-Dimensional Chemical Structures Representation and Searching of Molecular Electrostatic Potentials Using Field-Graphs. 

The prediction of three-dimensional chemical structure from a list of atoms in a molecule and their connectivity is a good example of a chemical problem that may be solved by an expert system. We have already seen (Fig. 9.2) how the SMILES interpreter can construct a two-dimensional representation of a structure from its one-dimensional representation as a SMILES string. The CONCORD program (CONnection table to CoORDinates) takes a SMILES string and, very rapidly, produces a three-dimensional model of an input molecule. This system is a hybrid between an expert system and a molecular mechanics program, molecular mechanics being the method by which molecular structures are minimized in most molecular modelling systems. The procedure operates as follows. 

The design motif for this book cover consists of some examples of molecules discussed in the chapters floating above a representation of water, land, and sky. The artwork was provided by David H. Lipnick, a student in the School of the Arts at Virginia Commonwealth University, and the three-dimensional chemical structures generated by Robert L. Lipnick. 

There are a number of different ways that the molecular graph can be conununicated between the computer and the end-user. One common representation is the connection table, of which there are various flavours, but most provide information about the atoms present in the molecule and their connectivity. The most basic connection tables simply indicate the atomic number of each atom and which atoms form each bond others may include information about the atom hybridisation state and the bond order. Hydrogens may be included or they may be imphed. In addition, information about the atomic coordinates (for the standard two-dimensional chemical drawing or for the three-dimensional conformation) can be included. The connection table for acetic acid in one of the most popular formats, the Molecular Design mol format [Dalby et al. 1992], is shown in Figure 12.3. 

Three-Dimensional Modeling of Chemical Structures. The two-dimensional representations of chemical stmctures are necessary to depict chemical species, but have limited utiHty in providing tme understanding of the effects of the three-dimensional molecule on properties and reactive behavior. To better describe chemical behavior, molecular modeling tools that reflect the spatial nature of a given compound are required. 

Figure 9.10 Three-dimensional representation of the data volume of a tryptic digest of ovalbumin. Series of planar slices through the data volume produce stacks of disks in order to show peaks. Reprinted from Analytical Chemistry, 67, A. W. Moore Jr and J. W. Jorgenson, Comprehensive three-dimensional separation of peptides using size exclusion chromatogra-phy/reversed phase liquid chromatography/optically gated capillary zone electrophoresis, pp. 3456-3463, copyright 1995, with permission from the American Chemical Society.

In chemistry, perhaps because of the significance in visualizing molecular strac-ture, there has been a focus on how students perceive three-dimensional objects from a two-dimensional representation and how students mentally manipulate rotated, reflected and inverted objects (Stieff, 2007 Tuckey Selvaratnam, 1993). Although these visualization skills are very important in chemistry, it is evident that they are not the only ones needed in school chemistry (Mathewson, 1999). For example, conceptual understanding of nature of different types of chemical bonding, atomic theory in terms of the Democritus particle model and the Bohr model, and... 

The importance of methods to predict log P from chemical structure was described in Chapter 14, which is focused on fragment- and atom-based approaches. In this chapter property-based approaches are reviewed, which comprise two main categories (i) methods that use three-dimensional (3D) structure representation and (ii) methods that are based on topological descriptors. 

FIGURE 1.3 Three-dimensional representation of a tryptic digest of ovalbumin. The three-dimensional separation consists of size-exclusion chromatography (first dimension), reversed-phase LC (second dimension), and capillary electrophoresis (third dimension). From Moore and Jorgenson, (1995) with permission of the American Chemical Society. 

Wipke, W. T. "Computer-Assisted Three-Dimensional Synthetic Analysis . In Computer Representation and Manipulation of Chemical Information Wipke, W. T. Heller, S. R. Feldmann, R. J. Hyde, E., Eds. John Wiley and Sons, Inc. 1974, pp 147-174. 

It is estimated that far more than 50% of the published chemical literature concerns heterocyclic structures. One striking structural feature inherent to heterocycles, which continues to be exploited to great advantage by the drug industry, lies in their ability to manifest substituents around a core scaffold in a defined three-dimensional representation, thereby allowing for far fewer degrees of conformational freedom than the corresponding conceivable acyclic structures. 

In chemoinformatics research, partitioning algorithms are applied in diversity analysis of large compound libraries, subset selection, or the search for molecules with specific activity (1-4). Widely used partitioning methods include cell-based partitioning in low-dimensional chemical spaces (1,3) and decision tree methods, in particular, recursive partitioning (RP) (5-7). Partitioning in low-dimensional chemical spaces is based on various dimension reduction methods (4,8) and often permits simplified three-dimensional representation of... 

The first task of chemoinformatics is to transform chemical knowledge, such as molecular structures and chemical reactions, into computer-legible digital information. The digital representations of chemical information are the foundation for all chemoin-formatic manipulations in computer. There are many file formats for molecular information to be imported into and exported from computer. Some formats contain more information than others. Usually, intended applications will dictate which format is more suitable. For example, in a quantum chemistry calculation the molecular input file usually includes atomic symbols with three-dimensional (3D) atomic coordinates as the atomic positions, while a molecular dynamics simulation needs, in addition, atom types, bond status, and other relevant information for defining a force field. 

---