Studies of nucleotide conformations and interactions. The relative stabilities of double‐helical B‐DNA sequence isomers

We present the results of molecular‐mechanics studies on base‐paired dinucleoside phosphates and hexanucleoside pentaphosphates. Starting from B‐DNA‐like conformations, we have refined the nucleic acid conformations, allowing all degrees of freedom to relax. The calculated energies of different base sequences are used to investigate the basis for the different stabilities of DNA polymers of different sequences, as found by Wells et al. [J. Mol. Biol. 54, 465–497, 1970]. Our calculations appear to reproduce the relative melting temperatures of sequence isomers as well or better than any of the previous calculations which addresssed the question of nucleotide stability. We offer a detailed physical explanation of three observations, that poly(dA)·poly(dT) melts higher than poly[d(A‐T)]·poly[d(A‐T)] by 6°C, that poly(dG)·poly(dC) melts lower than poly[d(G‐C)]·poly[d(G‐C)] by 12°C, and that poly(dA‐dG)·poly(dT‐dC) melts lower than poly(dA‐dC)·poly(dT‐dG) by 6°C. The dihedral angles found after refinement are similar to those of Levitt [Proc. Natl. Acad. Sci. USA 75, 640–644, 1978] and differ by ∼20° from the B‐DNA values. We also see evidence of base tilting and twisting similar to that found by Levitt. The two main differences in the results of our calculations and Levitt's lie in the sugar puckers [we find mainly C(2′)endo] and in the tendency to stay in local “torsional” minima (we find a number of examples of C(3′)endo sugar puckering and ω′ = trans rather than gauche). Both of these results are dependent on the nature of the potential function used in our study. However, our finding of movement from local torsional minima is suggestive of the significant flexibility of double‐stranded deoxynucleotides.

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