Table 1.
Sequences of the four studied DNA dodecamers, constituents of the sequence 601.
Fig 1.
BI and BII conformations in the B-DNA backbone.
Illustration of the BI ((ε-ζ) = -90°) and BII ((ε-ζ) = +100°) phosphate linkage conformations with a GpC dinucleotide extracted from MDs carried out with the Parmbsc0εζOLI (left) or CHARMM36 (right) force fields.
Fig 2.
Distribution of backbone (ε-ζ) values and 5’ sugar behavior in MD snapshots.
Top panels: the frequencies (N) of (ε-ζ) values were extracted from P-MDs (left panel, blue line) and C-MDs (right panels, red line) snapshots. The BI and BII regions are indicated, in accordance with the analysis presented in the main text. The hashed regions correspond to the distribution of ε/ζ:trans/trans, the categorization of which is ambiguous with regard to BI or BII. Bottom panels: pseudorotation phase angle (P) of the 5’ sugar puckers as a function of (ε-ζ) values (°), extracted from P-MDs (left panel) and C-MDs (right panel). The sugar ring conformations were in north (pseudorotation phase angle 0 to 50°), east (50 to 120°) or south (120 to 220°). The (ε-ζ) region assigned to BII does not contain 5’ north sugars. The color gradient is indicative of the density, with the highest densities in yellow. The vertical lines indicate the (ε-ζ) values used here to separate BI from BII in P- (blue lines) and C-MDs (red lines).
Table 2.
BII percentages from NMR compared to their simulated counterparts.
Fig 3.
Comparison between simulated and experimental BII percentages along the four dodecamers.
BII percentages (BII%) were plotted along the two complementary strands of each dodecamer sequence. BII% were extracted from P-MDs (left panels, blue) and C-MDs (right panels, red), or inferred from the 72 δPs collected by NMR (black). The error on BII% from NMR was estimated to be ±10%.
Table 3.
BII percentages from NMR compared to their simulated counterparts for selected steps.
Table 4.
Conformational combinations of facing phosphates in MDs.
Fig 4.
Conformational combinations of facing phosphate linkages illustrated with CHARMM36.
In C-MDs, the BII-rich facing phosphate linkages adopt three conformational combinations, BI•BI (grey), BI•BII|BII•BI (green) and BII•BII (violet). The course of these combinations versus time (ns) is illustrated for facing phosphate groups of Oligo 4, two BII-rich steps, C5pG6•C19pG20 and T7pA8•T17pA18, and one BI-rich step, G6pT7•A18pC19. For clarity, only a small part of the trajectory is shown here.
Fig 5.
Statistics on the transitions between the conformational states of facing phosphate groups.
The transitions between facing phosphate group combinations were analyzed for C5pG6•C19pG20 (grey) and T7pA8•T17pA18 (green) in Oligo 4, and C10pC11•G14pG15 (pink) in Oligo 2, from P-MDs (left) and C-MDs (right). These steps were chosen because they adopt BII•BII in the simulations. N% is the percentage of a transition type relative to the total number of transitions. The transition types are labeled as follow: 1: BI•BI → BI•BII|BII•BI or the inverse, BI•BII|BII•BI → BI•BI; 2: BI•BII|BII•BI → BII•BII or BII•BII → BI•BII|BII•BI; 3: BI•BII → BII•BI or BII•BI → BI•BII; 4: BI•BI → BII•BII or BII•BII → BI•BI.
Fig 6.
Facing phosphate states pair correlations.
The facing phosphate states BI•BII|BII•BI and BII•BII have probabilities Pi,j(BII•BI|BI•BII) (left panel) and Pi,j(BII•BII), (right panel), respectively, extracted from P-MDs (blue) and C-MDs (red) for each complementary step in the dodecamers. Pi,j(BII•BII) versus Pi(BII) Pj(BII) is not reported for P-MDs because of the much reduced BII•BII populations in these simulations. These Pi,j probabilities are compared to expressions containing the individual BII probabilities, Pi(BII) and Pj(BII), under the assumption that the conformational states of facing phosphate groups are independent of each other Eq 4 for Pi,j(BII•BI|BI•BII) and Eq 3 for Pi,j(BII•BII), see main text). The diagonal lines correspond to y = x.
Fig 7.
Quantification of the conformational combinations of independent facing phosphates based on NMR data.
The percentages of BI•BII|BII•BI (black bars) and BII•BII (grey bars) combinations (C%) of facing phosphates are plotted along the four dodecamer sequences. These percentages were calculated in the regime of independence of the conformational states of facing phosphates with Eqs 3 and 4 and the NMR data. The values are given in S1 Table.
Table 5.
Inter base pair parameters variations associated to the conformational states of the facing phosphate groups.
Fig 8.
Slide, Roll and Twist values generated by Parmbsc0εζOLI and CHARMM36 for individual complementary dinucleotide steps, versus the facing phosphate combinations.
The mean values of Slide, Roll and Twist were calculated over the MDs for each of the 36 complementary dinucleotides of the four dodecamers, categorized according to the BI•BI (grey squares), BI•BII|BII•BI (green circles) and BII•BII (violet triangles) combinations of their facing phosphate groups. The data were extracted from P-MDs and C-MDs, and time-averaged for each conformational combination. The standard deviations are 0.6 for slide, ~7° for roll and 6° for twist, with both force-fields. The correlation coefficients are 0.84 (P-slide versus C-slide), 0.90 (P-roll versus C-roll) and 0.78 (P-twist versus C-twist). The diagonal lines correspond to y = x.
Fig 9.
Variability of helical parameters depending on conformational combinations of facing phosphate linkages.
The standard deviations of slide (SDSlide), roll (SDRoll) and twist (SDTwist) associated to the three possible combinations of facing phosphates are shown for representative steps, CpG•CpG in P-MDs and C-MDs of Oligos 1, 3 and 4 (green), GpC•GpC in P-MDs of Oligos 1, 2, 3 and 4 (violet) and TpA•TpA in C-MDs of Oligos 1, 3 and 4 (orange). Steps with the largest sampling of BII•BII (1.1 to 2.9%), were selected from P-MDs and C-MDs (7.5 to 21.8%). Top panels: P-MDs; bottom panels: C-MDs.