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

Abstract

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: ε (t), ζ(t), α(+), β(–ac), and γ(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.