Ensemble distance geometry method

The ensemble distance geometry pharmacophore modeling approach of Sheridan et al. (145) provides the most direct and efficient method for... 

By examining the stmctures of the two microcystins as derived from the distance geometry calculations, many of the NOES could not be described using the standard method of applying the NOEs to one conformation. Distance violations approaching 1.0 A were observed, particularly for the residues located around the Mdha residue. The constraint that this residue introduces into the cyclic peptide is significant, and it could very well be the source of dynamics, fast on the NMR time-scale. With this in mind, we undertook the calculation of these two inhibitors of the protein phosphatases 1 and 2A using the ensemble approach. 

Each program was used to generate conformational ensembles for the compounds in the data set. To find out whether the conformational search method under consideration is able to reproduce biologically active conformations within the ensembles of conformations, the computed conformations were compared to their x-ray geometries (receptor-bound conformations) by applying a distance measure in Cartesian space (i.e., the RMS rz deviation of the corresponding atoms). 

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