STRUCTURE AND CONFORMATIONAL DYNAMICS OF (DA-CENTER-DOT-DT-DT)(6) WITH PARALLEL THYMINE CHAINS

Optimization of intramolecular energy and nanosecond molecular-dynamic s simulation were performed for a hexameric fragment of triple-strande d helix (dA.dT:dT)(6) with parallel thymine chains, considering both b asic schemes of hydrogen bonding in triples. interactions of thymine o xygens were shown to be decisive for the characteristic tripling in pa rallel helices whereby the third-chain thymines form hydrogen bonds wi th both Watson-Crick bases, At equilibirum, A-type conformers dominate in the purine chain (95% of common time), while both thymine chains s pend roughly equal time in A and B conformations, with the only differ ence that conformers with E-type sugar rings are more frequent for the Third chain. The third chain conformation at potential energy minimum is clearly irregular. Nonetheless, the helix parameters, especially i ts pitch, are virtually independent of the dynamic conformational chan ges. The patterns governing correlated atomic movements were defined. The data suggest that the probability of parallel dA.dT:dT triplexes w ould drop steeply with increasing oligonucleotide length. The relative stability of parallel and antiparallel triplexes is discussed.