Where Do Distance Constraints Come from

Many other intermolecular and intramolecular contacts are described by distances (hydrogen bond lengths, van der Waals contact, experimentally determined distances from nuclear Overhauser effect (NOE) spectra, fluorescence energy transfer, etc.) so that the distance matrix representation can be used to specify all the known information about a molecular structure. These bounds are entered into a distance geometry program, as are other bounds that specify constraints on modeling problems, such as constraints to superimpose atoms in different molecules. Hypotheses about intra- or intermolecular conformations and interactions are easily specified with distance constraints models can be built quickly to test different hypotheses simply by changing the distance constraints. 

All possible conformers lie between these upper and lower distance bounds—the task of distance geometry is to convert or embed this usually uncertain distance information into accurate three-dimensional Cartesian coordinates. Crippen and HavePi solved the problem for the case of an exact distance matrix, where all distances are known. Much additional effort has gone into finding efficient and practical methods for solving the general problem of a distance bounds matrix, where only a subset of the distances is known exactly. This remains a very difficult problem for large molecules with more than 1000 atoms. 

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