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(TTTTTT)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 RP methylation predominantly influences the conformation around the bond (PO3), while SP methylation mostly changes the conformation (PO5). 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-SP oxygen is most available in a right-handed helix, we suggest changes around the 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)