Stability and cooperativity of nucleic acid base triplets.

Geometries and stabilities of various base triplets have been studied using ab initio quantum chemical methods. Their optimized geometries are determined using the STO-3G basis set, and those of Hoogsteen and reverse Hoogsteen base pairs are evaluated with the 4-31G basis set. Moreover, the preferred hydrogen bond patterns of the bases in triple helices are discussed. A cooperative effect for base pairing in triplets is presented, and it can be either positive or negative. Almost all base triplets that contain Watson-Crick G:C base pairs show a positive cooperativity. Conversely, the base triplets with Watson-Crick A:T base pairs mostly display a negative cooperativity. The interaction energies of base triplets are reported and the relative stabilities of base triplets are found as follows: A+.GC > C+.GC(H) > C+.GC(rH) > G.GC(H) > G.GC(rH) > A.GC > T.AT(rH) > U.AU(H) > U.AT(H) > A.AT > G.AT > T.AT(m) > G.TA(2) > G.TA(1) H and rH denote the Hoogsteen and reverse Hoogsteen positions of the third base that would lead to parallel and antiparallel orientations respectively of the third chain with respect to the Watson-Crick paired purine chain. 'm' denotes the middle pairing scheme, in which the third base hydrogen bonds to both bases of Watson-Crick pair.