Conformational analysis distance geometry

Comparative Molecular Field Analysis (CoMFA) Conformational Flexibility in 3D Structure Searching Conformational Sampling Distance Geometry Theory, Algorithms, and Chemical Applications Free Energy Calculations Methods and Applications Free Energy Perturbation... 

With the development of accurate computational methods for generating 3D conformations of chemical structures, QSAR approaches that employ 3D descriptors have been developed to address the problems of 2D QSAR techniques, e.g., their inability to distinguish stereoisomers. The examples of 3D QSAR include molecular shape analysis (MSA) [34], distance geometry [35,36], and Voronoi techniques [37]. 

If all nuclei are assigned and the spectral parameters for the conformational analysis are extracted, a conformation is calculated - usually by distance geometry (DG) or restrained molecular dynamics calculations (rMD). A test for the quality of the conformation, obtained using the experimental restraints, is its stability in a free MD run, i.e. an MD without experimental restraints. In this case, explicit solvents have to be used in the MD calculation. An indication of more than one conformation in fast equilibrium can be found if only parts of the final structure are in agreement with experimental data [3]. Relaxation data and heteronuclear NOEs can also be used to elucidate internal dynamics, but this is beyond the scope of this article. 

Finally, Burkhard Luy, Andreas Frank and Horst Kessler discuss Conformational Analysis of Drugs by Nuclear Magnetic Resonance Spectroscopy . The determination and refinement of molecular conformations comprehends three main methods distance geometry (DG), molecular dynamics (MD) and simulated anneahng (SA). In principle, it is possible to exclusively make use of DG, MD or... 

Spellmeyee, D.C., Wong, A.K., Bower, M.J., and Bianey, J.M. Conformational analysis using distance geometry methods./. Mol. Graph. Model. 1997, 35, 18-36. 

E. Peggion, A. Bisello, M. Rosenblatt, M. Chorev, D. F. Mierke, Mono- and bicyclic analogs of parathyroid hormone-related protein. 2. Conformational analysis of antagonists by CD, NMR, and distance geometry calculations, Biochemistry 1997, 36, 3300-3307. 

Weiner et al. (32) have described the application of distance geometry to the conformational analysis of cyclooctane, cyclododecane, 18-crown-6, and... 

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. 

Distance geometry Distance geometry pioneered by G.M. Crippen is a method for converting a set of distance bounds into a set of coordinates that are consistent with these bounds. In applying distance geometry to conformationally flexible structures the upper and lower bounds to the distance between each pair of points (atoms) are used. This approach is useful for molecular modelbuilding and conformational analysis and has been extended to find a common pharmacophore from a set of biologically active molecules. 

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