Optimisation of metric matrix embedding by genetic algorithms.

To improve the convergence properties of 'embedding' distance geometry, a new approach was developed by combining the distance-geometry methodology with a genetic algorithm. This new approach is called DG-OMEGA (DG omega, optimised metric matrix embedding by genetic algorithms). The genetic algorithm was used to combine well-defined parts of individual structures generated by the distance-geometry program, and to identify new lower and upper distance bounds within the original experimental restraints in order to restrict the sampling of the metrisation algorithm to promising regions of the conformational space. The algorithm was tested on cyclosporin A, which is notorious for its intrinsic difficult sampling properties. A set of 58 distance restraints was employed. It was shown that DG omega resulted in an improvement of convergence behaviour as well as sampling properties with respect to the standard distance-geometry protocol.

Optical design with the aid of a genetic algorithm.

Natural evolution is widely accepted as being the process underlying the design and optimization of the sensory functions of biological organisms. Using a genetic algorithm, this process is extended to the automatic optimization and design of optical systems, e.g. as used in astronomical telescopes. The results of this feasibility study indicate that various types of aberrations can be corrected quickly and simultaneously, even on small computers.

Conformational analysis of a dinucleotide photodimer with the aid of the genetic algorithm.

The solution structure of the photodimer cis,syn-dUp[]dT is derived with the aid of the genetic algorithm. The conformational space available for the molecule is sampled efficiently using the computer program DENISE and tested against a set of constraints available from nmr experiments. The dominant conformation in solution found with this approach can be described by the following combinations of sugar-phosphate backbone torsion angles: epsilon(t), zeta(t), alpha(+), beta(-ac), and gamma(t). The conformation of the sugars and glycosidic torsion angles are S type and syn, respectively. The cyclobutane ring and pyrimidines are puckered. In addition, other conformations that exist in equilibrium with the first are found. It is concluded that the cyclobutane-pyrimidine system is rigid, whereas the sugar-phosphate backbone is flexible. The solution structures are compared with the crystal structure of the strongly related cyano-ethyl ester of cis,syn-dTp[]dT.