A Comparative Study of the DG-OMEGA (DG), DGII, and GAT Method for the Structure Elucidation of a Methylene-acetal Linked Thymine Dinucleotide

Abstract This research continues the investigation of the properties of the recently developed structure elucidation method DG-OMEGA (DGΩ). Towards this end it was applied for the structure determination of a methylene-acetal linked thymine dinucleotide. The performance of DGΩ was compared to the well-established DGII method, and to a genetic algorithm for structure determination in torsion angle space (GAT). Conformations that resulted from these methods were compared before and after a restrained energy minimisation, which included an all-atom AMBER force field. From the present study it was concluded that the sampling and convergence properties of DGΩ for this target molecule were slightly better than for DGII. DGΩ required, however, substantially more computational effort than DGII to arrive at a set of conformations. The GAT method resulted in conformations of inferior quality compared with the DGII and DGΩ structures, but a better defined covalent geometry. More importantly, it was established that the length of the simulated annealing refinement could not be reduced significantly in comparison to DGII despite that, within DGΩ, DGII is iterated by the genetic algorithm. A reduced refinement in DGΩ led to conformations with distorted covalent geometries.

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