*Algorithm Forgeneration O the Most Representative Structures (MRS)

Supporting materials

Figure S1. Energetic characteristics of probing distribution sets estimated for each of dinucleotide steps belonging to central telomeric triad of all four analyzed oligonucleotides. Algorithm was presented below in the footnote*. Symbol S1 stands for free non-modified B-DNA telomeric repeat unit d(A1G2G3G3T5T6) taken from central part of modelled 14-mer in water solution, S2 represents oxidized analogue d(A1G2Z3G4T5T6), S3denotes non-oxidized telomere oligomer in complex with TRF1 and S4 refers to oxidized telomeric fragment bound to TRF1. Symbol Z stands for guanine (in case of S1 and S3) or 8-oxoguanine (for S2 and S4). Gray lines correspond to different probing sets of 36 structures, red linesrepresented averaged distributions (over 360 structures) and blue lines denotes selected the most representative set of structures used for further intermolecular interaction energies (IIE) estimation on ab initio level. All IIE values were estimated using Amber forcefield.

d(G2pG3) of S1 / d(G3pG4) of S1
d(G2pZ3) of S2 / d(Z3pG4) of S2
d(G2pG3) of S3 / d(G3pG4) of S3
d(G2pZ3) of S4 / d(Z3pG4) of S4

*Algorithm forgeneration o the most representative structures (MRS):

the distributions of base step parameters (shift, slide, rise, roll, tilt and twist) were extracted from MD trajectories based on X3DNA program [53];
after normalisation of all values corresponding histograms were prepared for each base step parameter (after division of the whole span of values (from 0 to 1) into six equal intervals);
obtained population percentages were used as weighting coefficient for selection of six conformations for each parameter (thus in total 36 structures for each dinucleotide step);
the probing distribution sets were generated by random selection of structures in number corresponding to weighting coefficients;
ten probing distribution sets were obtained and IIE values were estimated for each conformation based on Amber forcefield [55];
obtained IIE distributions were presented in the form of histograms and most representative structures were defined as those probing distribution sets for which shapes of IIE histograms was closed to the averaged one (according to calculated RMSD values).

Figure S2. Median values of base pair parameters distributions estimated for trajectories collected during 20x2ns MD runs. Chains notation is the same as in Fig. S1. Solid lines with black symbols characterize CTT (central telomeric triad), while gray lines denote the rest of pairs within telomere repeat unit. For clarity, the magnitudes of standard derivations were indicated only for pairs involving Z3 purine.

displacement parameters [Å] / angular parameters [°]

Figure S3. Median values of base step parameters distributions estimated for trajectories collected during 20x2ns MD runs. Notation is the same as in Fig.S1.

displacement parameters [Å] / angular parameters [°]

Table S1. Statistical characteristics of base pair parameters distributions for all pairs constituting telomere repeat unit in analyzed oligonucleotide chains. For notation refer to Fig.S1

S1 / S2 / S3 / S4
M±SD / K / S / M±SD / K / S / M±SD / K / S / M±SD / K / S
A1 / Buckle / 4.06 ± 11.25 / 0.04 / -0.08 / 4.81 ± 11.10 / 0.09 / -0.14 / -1.57 ± 11.74 / -0.05 / -0.09 / -3.72 ± 12.41 / 0.09 / -0.10
G2 / 11.82 ± 9.59 / 0.06 / -0.11 / 10.80 ± 9.08 / 0.10 / -0.08 / 6.37 ± 9.51 / 0.12 / -0.09 / 4.56 ± 9.50 / 0.02 / -0.08
Z3 / 3.88 ± 10.27 / 0.00 / -0.02 / 7.56 ± 10.28 / -0.03 / 0.03 / 5.40 ± 10.79 / 0.23 / -0.29 / 5.67 ± 10.96 / 0.02 / -0.10
G4 / -11.23 ± 9.88 / 0.04 / 0.20 / -7.24 ± 10.83 / -0.14 / 0.12 / -1.40 ± 10.85 / -0.15 / 0.09 / -0.11 ± 11.16 / 0.01 / -0.09
T5 / -13.00 ± 9.86 / -0.21 / 0.05 / -10.95 ± 9.97 / -0.04 / 0.06 / -5.26 ± 10.01 / 0.07 / 0.06 / -6.28 ± 9.43 / 0.13 / 0.08
T6 / -8.25 ± 10.64 / 0.21 / -0.03 / -8.33 ± 10.82 / 0.23 / 0.08 / 0.54 ± 12.39 / 0.12 / -0.04 / -0.91 ± 11.52 / 0.11 / 0.08
A1 / Opening / 2.15 ± 6.14 / 2.28 / 0.52 / 2.62 ± 6.38 / 4.28 / 0.95 / 0.87 ± 6.14 / 1.09 / 0.15 / 2.97 ± 6.62 / 1.90 / 0.49
G2 / 1.97 ± 3.29 / 1.02 / 0.25 / 2.25 ± 3.33 / 0.89 / 0.30 / 1.19 ± 3.58 / 1.87 / 0.09 / 1.87 ± 3.68 / 0.86 / 0.26
Z3 / 2.28 ± 3.32 / 3.04 / 0.60 / 1.37 ± 3.43 / 5.67 / 0.78 / 0.96 ± 3.39 / 0.39 / 0.10 / 0.20 ± 3.40 / 2.01 / -0.07
G4 / 2.24 ± 5.64 / 7.96 / -2.07 / 2.73 ± 3.51 / 6.31 / 0.85 / 1.30 ± 3.33 / 0.44 / 0.09 / 1.50 ± 3.58 / 0.76 / 0.12
T5 / 0.51 ± 6.38 / 2.20 / -0.79 / 1.02 ± 5.15 / 0.51 / 0.15 / 1.91 ± 5.15 / 0.47 / 0.05 / 1.77 ± 5.48 / 0.63 / 0.12
T6 / 1.71 ± 6.30 / 1.67 / -0.11 / 2.33 ± 5.86 / 3.95 / 0.80 / 3.13 ± 5.14 / 1.34 / 0.31 / 3.37 ± 5.12 / 1.31 / 0.51
A1 / Propeller / -5.95 ± 8.13 / 0.30 / -0.08 / -5.89 ± 8.49 / 0.60 / -0.06 / -9.81 ± 8.50 / 0.00 / -0.10 / -10.34 ± 8.73 / 0.11 / -0.12
G2 / -6.54 ± 7.81 / 0.13 / 0.06 / -8.15 ± 7.51 / 0.08 / 0.02 / -9.17 ± 8.29 / -0.03 / 0.00 / -11.38 ± 8.35 / 0.00 / 0.05
Z3 / -11.76 ± 7.88 / 0.27 / 0.10 / -11.63 ± 8.25 / 0.15 / 0.17 / -7.82 ± 9.50 / 0.45 / 0.45 / -7.32 ± 9.72 / -0.01 / 0.13
G4 / -15.91 ± 7.77 / 0.26 / 0.19 / -15.42 ± 7.74 / 0.19 / 0.15 / -11.80 ± 8.70 / -0.05 / 0.21 / -14.76 ± 7.31 / 0.06 / 0.00
T5 / -14.28 ± 7.59 / 0.23 / 0.10 / -15.37 ± 7.66 / 0.18 / 0.13 / -13.29 ± 8.32 / -0.08 / -0.01 / -15.20 ± 7.90 / 0.05 / 0.03
T6 / -8.02 ± 8.57 / 0.19 / 0.08 / -10.07 ± 8.47 / 0.10 / -0.01 / -7.37 ± 10.65 / -0.13 / 0.09 / -6.86 ± 9.20 / 0.17 / -0.01
A1 / Shear / -0.05 ± 0.29 / 0.04 / 0.08 / -0.06 ± 0.29 / 0.08 / 0.05 / -0.06 ± 0.30 / 0.03 / 0.13 / -0.08 ± 0.30 / 0.05 / 0.05
A1 / -0.19 ± 0.32 / 0.22 / -0.03 / -0.18 ± 0.32 / 0.19 / -0.07 / -0.16 ± 0.31 / -0.01 / 0.01 / -0.15 ± 0.32 / 0.10 / -0.02
Z3 / -0.29 ± 0.32 / 0.66 / -0.07 / -0.26 ± 0.33 / 0.95 / -0.04 / -0.28 ± 0.34 / 0.10 / 0.13 / -0.27 ± 0.34 / 0.20 / 0.07
G4 / -0.28 ± 0.32 / 0.42 / -0.09 / -0.24 ± 0.32 / 1.53 / -0.22 / -0.17 ± 0.33 / 0.90 / 0.18 / -0.13 ± 0.32 / 1.16 / 0.28
T5 / 0.01 ± 0.27 / 0.06 / -0.06 / 0.01 ± 0.27 / -0.02 / -0.06 / -0.05 ± 0.28 / 0.20 / -0.08 / -0.06 ± 0.28 / 0.11 / -0.05
T6 / 0.05 ± 0.28 / 0.01 / -0.05 / 0.05 ± 0.28 / 0.01 / -0.04 / -0.07 ± 0.27 / 0.07 / -0.06 / -0.07 ± 0.27 / -0.01 / -0.06
A1 / Stagger / 0.08 ± 0.42 / 0.15 / 0.07 / 0.12 ± 0.42 / 0.09 / 0.01 / 0.09 ± 0.43 / 0.12 / 0.09 / 0.18 ± 0.45 / 0.01 / 0.03
G2 / 0.27 ± 0.40 / 0.08 / 0.00 / 0.28 ± 0.38 / 0.19 / 0.07 / 0.21 ± 0.38 / 0.09 / 0.00 / 0.18 ± 0.37 / 0.08 / 0.05
Z3 / 0.02 ± 0.41 / 0.23 / 0.18 / 0.09 ± 0.41 / 0.38 / 0.23 / 0.08 ± 0.45 / 0.22 / 0.11 / 0.00 ± 0.45 / 0.29 / 0.16
G4 / -0.08 ± 0.37 / 0.36 / 0.10 / -0.04 ± 0.38 / 0.22 / 0.12 / 0.12 ± 0.44 / 0.29 / 0.03 / 0.16 ± 0.43 / 0.49 / 0.27
T5 / 0.11 ± 0.39 / 0.21 / 0.08 / 0.09 ± 0.40 / 0.07 / 0.05 / 0.15 ± 0.44 / 0.04 / 0.01 / 0.12 ± 0.43 / 0.11 / 0.09
T6 / -0.06 ± 0.40 / 0.18 / -0.01 / -0.10 ± 0.42 / 0.17 / 0.05 / -0.15 ± 0.44 / 0.10 / -0.08 / -0.17 ± 0.43 / 0.11 / 0.04
A1 / Stretch / 0.05 ± 0.13 / 6.52 / 1.25 / 0.05 ± 0.14 / 6.75 / 1.29 / 0.02 ± 0.13 / 2.86 / 0.75 / 0.03 ± 0.14 / 4.21 / 0.98
G2 / 0.00 ± 0.12 / 0.97 / 0.37 / 0.00 ± 0.12 / 1.16 / 0.46 / -0.03 ± 0.12 / 1.32 / 0.45 / -0.01 ± 0.13 / 1.37 / 0.57
Z3 / -0.05 ± 0.12 / 2.17 / 0.49 / -0.05 ± 0.12 / 3.13 / 0.56 / -0.06 ± 0.12 / 0.65 / 0.17 / -0.08 ± 0.12 / 0.77 / 0.06
G4 / -0.03 ± 0.16 / 6.35 / -1.05 / -0.02 ± 0.12 / 4.49 / 0.79 / -0.04 ± 0.12 / 0.78 / 0.24 / -0.03 ± 0.12 / 1.26 / 0.38
T5 / 0.06 ± 0.14 / 2.13 / 0.12 / 0.05 ± 0.12 / 1.07 / 0.49 / 0.04 ± 0.12 / 1.72 / 0.55 / 0.04 ± 0.13 / 2.48 / 0.76
T6 / 0.05 ± 0.14 / 3.13 / 0.31 / 0.05 ± 0.14 / 14.47 / 1.61 / 0.04 ± 0.13 / 3.82 / 0.79 / 0.04 ± 0.12 / 1.95 / 0.59

M – median value, SD – standard deviation, K – kurtosis, S – skewness

Table S2. Statistical characteristics of base step parameters distributions for all pairs constituting telomere repeat unit in analyzed oligonucleotide chains. For notation refer to Fig.S1

S1 / S2 / S3 / S4
M±SD / K / S / M±SD / K / S / M±SD / K / S / M±SD / K / S
A1/G2 / Rise / 3.15 ± 0.30 / 0.53 / 0.33 / 3.17 ± 0.28 / 0.42 / 0.28 / 3.16 ± 0.30 / 0.31 / 0.31 / 3.15 ± 0.29 / 0.35 / 0.25
G2/Z3 / 3.48 ± 0.31 / 0.20 / 0.24 / 3.39 ± 0.32 / 0.15 / 0.22 / 3.39 ± 0.32 / 0.38 / 0.36 / 3.36 ± 0.32 / 0.30 / 0.32
Z3/G4 / 3.64 ± 0.32 / 0.10 / 0.12 / 3.59 ± 0.31 / 0.20 / 0.22 / 3.52 ± 0.36 / 0.13 / 0.21 / 3.50 ± 0.36 / 0.60 / 0.39
G4/T5 / 3.38 ± 0.27 / 0.71 / 0.29 / 3.41 ± 0.28 / 0.36 / 0.26 / 3.47 ± 0.28 / 0.25 / 0.31 / 3.48 ± 0.29 / 0.80 / 0.36
T5/T6 / 3.20 ± 0.27 / 0.42 / 0.34 / 3.23 ± 0.28 / 5.42 / 0.79 / 3.20 ± 0.29 / 2.41 / 0.48 / 3.20 ± 0.27 / 0.44 / 0.33
A1/G2 / Roll / 2.10 ± 5.57 / 1.23 / 0.30 / 2.31 ± 5.60 / 0.40 / 0.12 / 2.04 ± 5.00 / 0.13 / 0.04 / 2.70 ± 5.34 / 0.23 / 0.00
G2/Z3 / 4.37 ± 5.21 / 0.47 / -0.12 / 4.79 ± 5.36 / 0.43 / -0.11 / 0.83 ± 5.94 / 0.23 / -0.16 / 0.64 ± 5.93 / 0.16 / -0.08
Z3/G4 / 6.10 ± 4.88 / 0.28 / -0.07 / 5.57 ± 5.14 / 0.27 / -0.07 / 0.78 ± 5.43 / 0.10 / -0.13 / 0.22 ± 5.41 / 0.05 / -0.07
G4/T5 / 0.10 ± 4.49 / 0.29 / -0.07 / 0.05 ± 4.52 / 0.32 / -0.09 / -3.11 ± 4.39 / 0.21 / -0.21 / -2.72 ± 4.61 / 0.47 / -0.28
T5/T6 / 0.21 ± 5.54 / 0.28 / 0.03 / 0.62 ± 5.60 / 0.48 / 0.08 / -2.16 ± 5.59 / 0.80 / -0.01 / -1.58 ± 5.77 / 0.19 / -0.21
A1/G2 / Shift / 0.01 ± 0.84 / -0.46 / -0.16 / -0.66 ± 0.72 / 0.05 / 0.30 / -0.02 ± 0.73 / -0.39 / -0.01 / -0.54 ± 0.72 / -0.18 / 0.31
G2/Z3 / 0.13 ± 0.68 / -0.17 / -0.05 / 0.70 ± 0.55 / 0.18 / 0.10 / 0.58 ± 0.73 / -0.54 / -0.15 / 1.11 ± 0.55 / 0.78 / -0.41
Z3/G4 / -0.02 ± 0.58 / 0.32 / -0.30 / -0.30 ± 0.72 / -0.26 / 0.06 / -0.11 ± 0.69 / 0.34 / -0.02 / -0.46 ± 0.60 / -0.21 / 0.01
G4/T5 / -0.46 ± 0.55 / 0.17 / 0.24 / -0.35 ± 0.57 / 0.06 / 0.27 / -0.33 ± 0.47 / 0.10 / 0.10 / -0.26 ± 0.50 / 0.63 / 0.39
T5/T6 / 0.56 ± 0.70 / -0.26 / -0.24 / 0.47 ± 0.69 / -0.38 / -0.13 / 0.94 ± 0.68 / -0.14 / -0.18 / 1.04 ± 0.62 / 1.80 / -0.73
A1/G2 / Slide / -0.43 ± 0.69 / -0.44 / -0.18 / -0.09 ± 0.61 / 0.48 / -0.56 / -0.14 ± 0.60 / -0.27 / -0.18 / -0.01 ± 0.54 / 0.08 / -0.13
G2/Z3 / -1.10 ± 0.72 / -0.55 / 0.29 / -1.05 ± 0.69 / -0.40 / 0.30 / -0.25 ± 0.72 / -0.29 / -0.21 / -0.14 ± 0.69 / -0.38 / -0.27
Z3/G4 / -1.45 ± 0.59 / 1.24 / 0.92 / -0.97 ± 0.74 / -0.70 / 0.16 / -1.07 ± 0.77 / -0.11 / 0.59 / -0.26 ± 0.86 / -0.70 / -0.26
G4/T5 / -0.87 ± 0.45 / 0.37 / -0.29 / -0.87 ± 0.47 / 0.31 / -0.23 / -0.91 ± 0.53 / 0.71 / -0.58 / -0.93 ± 0.47 / 0.85 / 0.14
T5/T6 / -0.07 ± 0.54 / 0.12 / -0.44 / -0.14 ± 0.54 / 0.08 / -0.39 / 0.34 ± 0.59 / 0.38 / -0.50 / 0.44 ± 0.54 / 1.97 / -0.89
A1/G2 / Tilt / -2.63 ± 4.30 / 0.21 / 0.06 / -3.12 ± 4.21 / 0.21 / 0.02 / -0.97 ± 4.28 / 0.03 / 0.02 / -0.40 ± 4.57 / 0.02 / 0.08
G2/Z3 / 0.83 ± 4.44 / 0.07 / 0.07 / 1.63 ± 4.32 / 0.09 / 0.01 / 1.05 ± 4.56 / 0.00 / 0.03 / 3.44 ± 4.79 / 0.15 / 0.13
Z3/G4 / 0.72 ± 4.39 / 0.10 / -0.03 / -0.67 ± 4.56 / 0.00 / 0.02 / -1.04 ± 4.85 / 0.12 / -0.08 / -3.00 ± 5.05 / 0.10 / 0.09
G4/T5 / -0.16 ± 3.86 / 0.16 / -0.03 / 0.18 ± 3.87 / 0.11 / -0.05 / 0.90 ± 3.83 / 0.09 / 0.00 / 1.00 ± 4.07 / 0.15 / 0.00
T5/T6 / 2.60 ± 3.99 / 0.19 / 0.00 / 2.57 ± 4.01 / 0.26 / -0.04 / 3.32 ± 4.48 / 0.47 / 0.12 / 3.34 ± 4.27 / 0.58 / -0.01
A1/G2 / Twist / 30.66 ± 7.61 / -0.11 / -0.53 / 34.85 ± 5.17 / 0.00 / -0.49 / 30.42 ± 5.71 / -0.16 / -0.12 / 32.73 ± 5.57 / -0.27 / -0.21
G2/Z3 / 32.50 ± 5.51 / -0.21 / -0.02 / 27.36 ± 4.66 / 0.55 / -0.30 / 35.25 ± 5.37 / -0.14 / 0.02 / 30.77 ± 5.17 / -0.10 / -0.21
Z3/G4 / 32.41 ± 4.69 / 0.00 / 0.27 / 36.30 ± 5.49 / -0.34 / -0.07 / 33.25 ± 5.75 / 0.48 / -0.15 / 37.84 ± 5.77 / -0.31 / -0.05
G4/T5 / 34.57 ± 4.03 / 0.49 / -0.15 / 34.92 ± 3.98 / 0.23 / -0.06 / 34.51 ± 4.45 / -0.13 / 0.17 / 34.07 ± 3.67 / 0.44 / 0.19
T5/T6 / 36.15 ± 5.20 / 0.45 / -0.67 / 35.95 ± 5.51 / 0.13 / -0.55 / 37.12 ± 4.20 / 0.81 / -0.18 / 37.90 ± 4.06 / 0.84 / -0.32