Computational evaluation of the stability of 2'-O-methyl-RNA/RNA duplexes incorporating 3-deazaguanine derivatives by ab initio calculations and a molecular dynamics simulation

摘要: Abstract We evaluated the intrinsic interactions of guanine (G), 3-deazaguanine (c3G), and 2-N-acetyl-3-deazaguanine (a2c3G) with neighboring bases in 2′-O-methyl-RNA/RNA duplex, 5′-(C1G2G3C4X5A6G7G8A9G10)-3′/3′-r(G20C19C18G17C16U15C14C13U12C11)-5′, where X = G, c3G, or a2c3G. calculated energies using subsystems that were derived from averaged structure molecular dynamics (MD) trajectories duplexes by removing sugar phosphate moieties. The total vacuo revealed stability order was roughly a2c3G-C >> G-C > c3G-C, which not perfectly matched experimentally determined G-C > a2c3G-C >> c3G-C probably due to lack information on solvent effects. stacking c3G its smaller than those G because larger dipole moment whereas interaction a2c3G most cases increased overlapping area acetyl group moment. data also gave an insight into mechanism duplex stabilization compared c3G. In estimate effects, we conducted ab initio calculations some solute models.