Conformational Studies of Nucleic Acids: IV. The Conformational Energetics of Oligonucleotides: d(ApApApA) and ApApApA

Abstract

Utilizing a new method for modeling furanose pseudorotation (D. A. Pearlman and S.-H. Kim, J. Biomol. Struct. Dyn. 3, 85 (1985)) and the empirical multiple correlations between nucleic acid torsion angles we derived in the previous report (D. A. Pearlman and S.-H. Kim, previous paper in this issue), we have made an energetic examination of the entire conformational spaces available to two nucleic acid oligonucleotides: d(ApApApA) and ApApApA. The energies are calculated using a semi-empirical potential function. From the resulting body of data, energy contour map pairs (one for the DNA molecule, one for the RNA structure) have been created for each of the 21 possible torsion angle pairs in a nucleotide repeating unit. Of the 21 pairs, 15 have not been reported previously. The contour plots are different from those made earlier in that for each point in a particular angle-angle plot, the remaining five variable torsion angles are rotated to the values which give a minimum energy at this point. The contour maps are overall quite consistent with the experimental distribution of oligonucleotide data. A number of these maps are of particular interest: delta (C5'-C4'-C3'-O3')-chi (O4'-C1'-N9-C4), where the energetic basis for an approximately linear delta-chi correlation can be seen: zeta (C3'-O3'-P-O5')-delta, in which the experimentally observed linear correlation between zeta and delta in DNA(220 degrees less than zeta less than 280 degrees) is clearly predicted; zeta-epsilon (C4'-C3'-O3'-P), which shows that epsilon increases with decreasing zeta less than 260 degrees; alpha (O3'-P-O5'-C5')-gamma (O5'-C5'-C4'-C3') where a clear linear correlation between these angles is also apparent, consistent with experiment; and several others. For the DNA molecule studied here, the sugar torsion delta is predicted to be the most flexible, while for the RNA molecule, the greatest amount of flexibility is expected to reside in alpha and gamma. Both the DNA and RNA molecules are predicted to be highly polymorphic. Complete energy minimization has been performed on each of the minima found in the energy searches and the results further support this prediction. Possible pathways for B-form to A-form DNA interconversion suggested by the results of this study are discussed. The results of these calculations support use of the new sugar modeling technique and torsion angle correlations in future conformational studies of nucleic acids.

Molecular Dynamics of DNA: Comparison of Force Fields and Terminal Nucleotide Definitions

“…Therefore, considering that there is a smaller number of points in the graphics related to the GROMOS systems, one can conclude that the dispersion of the R/γ angles was indeed dramatically increased. Besides an extensive sampling of two local minima (g + /t and t/t), there was a significant population of the region g + /g -, which is described as an energetically disfavored region of the R/γ conformational landscape (5 kcal/mol 69 ). Also, since there is a "path" of points between the regions g + /t and t/t, there must be a very low energy barrier between these two states in the GROMOS force field, which allows the conformations to easily interconvert.…”

Geometrical and Electronic Structure Variability of the Sugar−phosphate Backbone in Nucleic Acids

“…They are characterized by the following average torsion angles: α = 299°, β = 179° (B II : β = 143°), γ = 48°, δ = 133° (B II : δ = 143°), ϵ = 182° (B II : ϵ = 251°), and ζ = 263° (B II : ζ = 168°). While the B I /B II conformational variability involving ϵ and ζ torsion angles was extensively studied both experimentally – and theoretically, – much less is known about the structural and energetic changes involving other torsion angles, such as the α and γ torsions. – However, the variations in these angles were shown to be important in complexes of DNA with ligands and proteins. – …”

“…While the B I /B II conformational variability involving and torsion angles was extensively studied both experimentally [46][47][48][49] and theoretically, [50][51][52] much less is known about the structural and energetic changes involving other torsion angles, such as the R and γ torsions. [53][54][55] However, the variations in these angles were shown to be important in complexes of DNA with ligands and proteins. [56][57][58][59][60][61][62][63] In addition, an occurrence of irreversible R/γ backbone flips in B-DNA simulations longer than 10 ns 21,64,65 was observed when AMBER ff94 or ff99 was used.…”

alpha/gamma Transitions in the B-DNA backbone

“…Pearlman and Kim (26) systematically explored the conformational space of backbone torsions in dA 4 and rA 4 and found a strong correlation between a and g using an energy contour map. Beyond the canonical a/g: g±/g+, they noted the existence of other minima, such as a/g: t/t, t/g+ and g+/t, on the potential energy surface (PES).…”