Other Methods for Generating Initial Structures

Distance geometry methods are certainly the most attractive means for generating initial structures in that they are now widely implemented, are relatively well understood, and reduce the tendency for an investigator to introduce biases into the structures. Some other methods should, however, be briefly mentioned. 

It is always possible to build a model of a molecule manually using interactive graphics either from scratch or based on a homologous molecule, but this method has not been used much in recent years by NMR spectrosco-pists. First, the sheer number of NMR restraints in a modern data set means that it will be technically difficult to produce a satisfactory structure. Second, the method relies on the ability of the investigator and will introduce any preconceptions of what the molecule should look like. Finally, the sampling properties of such an approach are almost nonexistent. 

Rather than manual model building, it is possible to use a database approach to build a starting structure from homologous structural fragments taken from the crystallographic protein data bank.37 The main use of this technique is that it can be used during the earliest investigations of a molecule when adequate NMR may not yet be available. 

Lastly, it should be mentioned that if a refinement method is very effective, the choice of a starting structure may be practically irrelevant. Some examples of this are listed under Refinement, Minimization, and Dynamics. 

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