Helix Morphology Changes in B-DNA Induced By Spontaneous B_I⇌B_IISubstate Interconversion

Abstract

Investigations of spontaneous, i.e. not forced, B-DNA's B(I)<==>B(II) substate transitions are carried out on the d(CGCGAATTCGCG)2 EcoRI dodecamer sequence using Molecular Dynamics Simulations. Analysis of the resulting transition processes with respect to the backbone angles reveals concerted changes not only for backbone angles epsilon, zeta, and beta, but also for the 5'-delta and 5'-chi angles. For alpha and delta inside the interconverting base step, a change is seen in short lived B(II) conformers. With respect to base morphology distinct changes are observed for buckle, propeller twist, shift, roll and twist, as well as x-displacement and tip. The base mainly involved in the changes is identified as the base preceding the interconverting phosphate. Altogether single B(I)<==>B(II) interconversions result only in local distortions represented by the larger spread of most parameters. Comparison of the atomic positional fluctuations derived from the simulation with those obtained from the static X-ray structure results in striking similarities.

Importance of Accurate DNA Structures in Solution: The Jun–Fos Model

“…4,5,18,41 Displacement of bases toward the major groove (more positive X-disp) is enhanced when several proximal phosphates are in BII and propagate to neighboring bases to maintain sufficient stacking. 19,50 Therefore, the global X-disp values are sensitive to the density of BII steps. In the simulations, the number of BII phosphates at any time varies and every MD snapshot can thus be characterized by its fraction of BII phosphates together with its global X-disp.…”

“…6 This is more than a physicochemical curiosity because the BI ↔ BII equilibrium is mechanically coupled to the DNA helicoidal parameters [e.g., roll, twist, and X-displacement (X-disp)] and therefore to its overall structure. [4][5][6][16][17][18][19] This may have general far-reaching implications for DNA-protein recognition. However, a practical and accurate characterization of these effects for DNA in solution has been lacking, if only because of difficulties in measuring the BII populations.…”

“…On the other hand, progress has recently been made in quantifying the populations of the DNA backbone BI and BII states by routine NMR in solution 6 on unlabeled DNA. These backbone states are sequence dependent and intimately coupled to the DNA helicoidal parameters, [4][5][6][16][17][18][19] which define much of DNA fine structure and intrinsic mechanical properties. It is therefore of great interest to investigate how the BI/BII populations can be used to aid in the refinement of DNA structures in solution, as addressed in the present work.…”

Sequence-Dependent DNA Flexibility Mediates DNase I Cleavage

“…40,45 Considering the phosphate group motion is of great interest because the BI ↔ BII equilibrium is intimately coupled to the deoxyribose conformational exchange 46,47 and to the DNA helicoidal parameters of twist, roll, slide, and basepair displacement (X-disp). 40,46,[48][49][50][51][52][53] The more a complementary dinucleotide favors the BII state, Fig. 1.…”

Modeling DNA Deformation

“…The B II state usually produces large twist and negative roll values of the corresponding step. [143][144][145] It is generally easier to find simultaneously two B II phosphates facing one another than at consecutive junctions in the same strand. 146 This can be explained by the fact that the base pair shift parameters anticorrelate between neighboring steps and hence the negative shift corresponding to B II state must be followed by a positive shift with a B I backbone.…”