What 3D Structures Do You Need

Fig- 7.3 Biotin in the conformation bound to streptavidin (PDB INQM) compared to a small-molecule X-ray stmcture from CSD (BIOTINIO), a single 3D structure generated 

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. 

Numerical methods. Computer-intensive numerical methods like quantum mechanics, molecular mechanics, or distance geometry [8] do not normally fall into the scope of automatic model builders. However, some model builders have built-in fast geometry optimization procedures or make use of distance geometry in order to generate fragment conformations. 

Clearly, there is no sharp border between all of the concepts discussed above. Most model builders try to use at least some of them in an efficient mixture in order to achieve the best compromise between computation times and quality. 

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