Vibrational normal modes and dynamical stability of DNA triplex poly(dA). 2poly(dT): S-type structure is more stable and in better agreement with observations in solution

A normal-mode and statistical mechanical calculation was carried out to determine the vibrational normal modes, contribution of internal fluctuations to the free energy, and hydrogen bond disruption of DNA triplex poly(dA).2poly(dT). The calculation was performed on both the x-ray fiber diffraction model with a N-type sugar conformation, and a newly proposed model with a S-type sugar conformation. Our calculated normal modes for the S-type structure are in better agreement with observed IR spectra for samples in D2O solution. We also find that the contribution of internal fluctuations to free energy, premelting hydrogen bond disruption probability, and hydrogen bond melting temperatures for the Hoogsteen and Watson-Crick hydrogen bonds all show that the S-type structure is dynamically more stable than the N-type structure in a nominal solution environment. Therefore our calculation supports experimental findings that the triplex d(T)n.d(A)nd(T)n most likely adopts a S-type sugar conformation in solution or at high humidity. Our calculations, however, do not preclude the possibility of an N-type conformation at lower humidities