Structure generation, automatic

This section describes briefly some of the basic concepts and methods of automatic 3D model builders. However, interested readers are referred to Chapter II, Section 7.1 in the Handbook, where a more detailed description of the approaches to automatic 3D structure generation and the developed program systems is given. 

Furthermore, the prediction of and NMR spectra is of great importance in systems for automatic structure elucidation. In many such systems, aU isomers with a given molecular formula are automatically produced by a structure generator, and are then ranked according to the similarity of the spectrum predicted for each isomer to the experimental spectrum. 

The missing link between the constitution of a molecule and its 3D structure in computahonal chemistry is a technique capable of automatically generating 3D models starhng from the connectivity information of a given molecule. Due to its basic role, 3D structure generation is one of the fundamental problems in computahonal chemistry. As a consequence, in recent years a number of automahc 3D model builders and conformer generators have become available. For two comprehensive reviews, see Refs. [3, 4]. 

Here, an attempt to classify different strategies to generate 3D molecular models is undertaken with the aim to specify the remit of methods which will be covered under the term automatic 3D structure generators . The focus will be on methods designed for small, dmg-like molecules. The prediction of the geometry of polymers, in parhcular of biopolymers, is a task of its own and not even attempted by the approaches discussed here. 

Conformation analysis methods. In many cases in the process of building a 3D structure from scratch, decisions have to be made between multiple alternatives with similar energy. A typical example is an sp -sp torsion angle with similar energies for the alternatives of -i-60°, -60° and 180°. In many cases, rules are used to decide (e.g. stretch an open chain portion as much as possible to avoid clashes). Sometimes, the best result cannot be determined without a conformation analysis (e.g. complex ring systems with exocycHc substituents). Despite conformation analysis being a topic of its own covered in the next chapter, many automatic 3D structure generators have to fall back in certain situations to a limited conformation search in order so solve a specific problem and to come up with a reasonable solution. 

High quality is one of the criteria defined in the requirements section above. Since the program should run automatically in batch mode, we mean by quality control an internal check of the 3D structures produced by the structure generator itself. In general, the abilities of a fast, automatic structure builder to assess the quaUty of its models are rather limited since, for example, an exhaustive conformation analysis and energy optimization is impossible in most cases. However, there are a Umited number of simple quaUty checks to avoid trivially distorted structures ... 

P. Eiseman, Automatic Structured Grid Generation, in CFD Review, M. Hafez and K. Oshima, eds., Wiley, New York, 1995,54. 

Distinct from these are automatic methods that directly transform 2D input information on atoms, bonds, and stereochemistry into 3D atomic coordinates. The automatic methods are classified into rule-based and data-based, fragment-based, conformational analysis, and numerical methods (Fig. 5). These classes of methods overlap more or less with each other and belong more or less to the domain of automatic 3D structure generation ... 

In this section, most of the currently available programs for automatic 3D structure generation will be discussed as far as they have been described in the literature. In addition, some early precursors of these methods are briefly presented due to their pioneering role in this field. 

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