Distance geometry method

The idea in Distance Geometry methods is that trial geometries can be generated from a set of lower and upper bounds on distances between all pairs of atoms. The method 

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Finding the minimum of the hybrid energy function is very complex. Similar to the protein folding problem, the number of degrees of freedom is far too large to allow a complete systematic search in all variables. Systematic search methods need to reduce the problem to a few degrees of freedom (see, e.g.. Ref. 30). Conformations of the molecule that satisfy the experimental bounds are therefore usually calculated with metric matrix distance geometry methods followed by optimization or by optimization methods alone. 

We have sequenced RpII and studied the structures of RpII and RpIII in solution by 2D-NMR and distance geometry methods. The resonances are almost completely assigned, and secondary and tertiary structures have been determined. Our results indicate that Rp toxins have a four strand anti-parallel )9-sheet and no a-helix. Functionally important residues are found to be located in looped regions of the... 

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. 

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. 

Aszodi, A, Taylor, W R. Folding polypeptide alpha-carbon backbones by distance geometry methods Biopolymers 1994 34, 489-505. 

There are several variations on die GA method, vaiyiiig die size uf die population, die The idea m Distance Geometry methods" " is that trial geometries can be generated from ... 

In the past, computational chemistry has been considered to be mainly synonymous with quantum chemistry. However, exciting developments of computational chemistry include molecular mechanics and dynamics applications to organic and biological molecules, computer graphics to study the properties of complex molecules, and distance geometry methods.. .. It is clear that a combination [of approaches] is more powerful than each is alone. 

Distance geometry methods tend to be faster than molecular mechanics methods and they are easier to parameterize. On the other hand, they are less accurate and the generated conformations can be rather crude because the distance matrix describes conformational properties only in a coarse manner as, for example, there is no possibility to describe multiple energy minima of torsional angles. Thus, the cyclohexane chair and boat conformations would be considered to be equally reasonable. 

To illustrate each of the steps in the distance geometry method, consider its application to a very simple molecule, pentane. Taking the standard carbon-carbon bond length to be 1.54 A and assuming tetrahedral geometry about each such atom, the following initial bounds matrix can be constructed (all values have been rounded to three decimal places) ... 

G. M. Clone, M. Nilges, A. T. Brtinger, M. Karplus, and A. M. Gronenborn, FEBS Lett., 213, 269 (1987). A Comparison of the Restrained Molecular Dynamics and Distance Geometry Methods for Determining Three-Dimensional Structures of Proteins on the Basis of Interproton Distances. 

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