Model building distance geometry

Define a crude initial structure by either distance geometry algorithms or by model building. The latter starts by defining elements of secundary structure (helices, 3 Sheets) fhom the NMR data. Even starting from an extended structure is feasible (53) ... 

Rubicon, a program for building 3D models using a distance geometry approach... 

Distance geometry can be used as a general model-building tool, as illustrated by O Neil and DeGrado (70) in their attempt at predicting the structure of... 

Another useful distance geometry model-building application is the elegant ensemble approach of Sheridan et al. (145), where multiple molecules are entered into a single distance bounds matrix. Intramolecular distance constraints are set as described in Section VII.A and mtermolecular distance constraints are entered to force specific intermolecular interactions to occur, for example, to superimpose a set of molecules using common functional groups. This approach is described in more detail in Section X.B on pharmacophore modeling. 

In general, five different approaches can be distinguished and are applied to explore the conformational space of a molecule systematic searches, rule-based and data-based approaches (model building), random methods, genetic algorithms, distance geometry, and simulation methods. Some of the basic principles and ideas behind these concepts have already been described in the Secs. 2 and 3 of this article. In the following, the application of these concepts to conformational analysis and searches will be discussed. 

Model building, in which molecular structure is represented by experimental data as input and this structure is manipulated with use of stereochemical rules. This includes computer graphics and distance geometry refinement. 

As a structure-generating tool, nab provides three methods for building models. They are rigid-body transformations, metric matrix distance geometry, and molecular mechanics. The first two methods are good initial methods, but almost always create structures with some distortion that must be removed. On the other hand, molecular mechanics is a poor initial method but very good at refinement. Thus the three methods work well together. 

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