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.