Molecular mechanics studies of parallel and antiparallel phosphate‐methylated DNA

Methylation of phosphate groups in oligo‐dT strands leads to a parallel duplex with T · T base pairs. Molecular mechanics calculations on parallel d() 2 show it to be a symmetric right‐handed helix with B‐DNA conformational characteristics. Phosphate methylation stabilizes the duplex by ca. 41 kcal/mol, due to removal of the interstrand phosphate electrostatic repulsions. The chirality introduced with phosphate methylation is important for the molecular geometry, since R P methylation predominantly influences the conformation around the ζ bond (PO 3′ ), while S P methylation mostly changes the α conformation (PO 5′ ). This is also true in antiparallel helices with methylated phosphates, as is shown by molecular mechanics calculations on d(GCGCGC) 2 . These results may be of relevance to protein–DNA interactions, where phosphate charges are also shielded. As the pro‐S P oxygen is most available in a right‐handed helix, we suggest changes around the α bond to occur upon protein complexation, leading to a widening of the major groove in the d(GCGCGC) 2 duplex (from 12 to 13 Å) and reduced minor groove (from 6 to 5 Å).