Limits...
μABC: a systematic microsecond molecular dynamics study of tetranucleotide sequence effects in B-DNA.

Pasi M, Maddocks JH, Beveridge D, Bishop TC, Case DA, Cheatham T, Dans PD, Jayaram B, Lankas F, Laughton C, Mitchell J, Osman R, Orozco M, Pérez A, Petkevičiūtė D, Spackova N, Sponer J, Zakrzewska K, Lavery R - Nucleic Acids Res. (2014)

Bottom Line: We demonstrate that the resulting trajectories have extensively sampled the conformational space accessible to B-DNA at room temperature.We confirm that base sequence effects depend strongly not only on the specific base pair step, but also on the specific base pairs that flank each step.By analyzing the conformation of the phosphodiester backbones, it is possible to understand for which sequences these substates will arise, and what impact they will have on specific helical parameters.

View Article: PubMed Central - PubMed

Affiliation: Section de Mathématiques, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.

Show MeSH

Related in: MedlinePlus

Non-Gaussian and multi-peaked helical parameter distributions. (a) Probability distributions of the inter-BP parameters for the central base pair step of the 136 distinct tetranucleotide sequences were inspected for visible deviations from Gaussian behavior. Helical parameters classed as ‘Multi-peaked’ (red) have two distinct peaks in their distributions for most flanking sequences. Monomodal distributions with obvious deviations from normality (such as pronounced shoulders or asymmetry) for most flanking sequences are classed as ‘Non-Gaussian’ (orange). The results are grouped on the basis of the purine/pyrimidine family of the dinucleotide step. Examples of parameter distributions (see also Figure 3) are shown for the twist of AGCA ((b), multi-peaked) and the shift of TGGT ((c), non-Gaussian).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4231739&req=5

Figure 4: Non-Gaussian and multi-peaked helical parameter distributions. (a) Probability distributions of the inter-BP parameters for the central base pair step of the 136 distinct tetranucleotide sequences were inspected for visible deviations from Gaussian behavior. Helical parameters classed as ‘Multi-peaked’ (red) have two distinct peaks in their distributions for most flanking sequences. Monomodal distributions with obvious deviations from normality (such as pronounced shoulders or asymmetry) for most flanking sequences are classed as ‘Non-Gaussian’ (orange). The results are grouped on the basis of the purine/pyrimidine family of the dinucleotide step. Examples of parameter distributions (see also Figure 3) are shown for the twist of AGCA ((b), multi-peaked) and the shift of TGGT ((c), non-Gaussian).

Mentions: The conclusions of our analysis are summarized in Figure 4 and can be compared with the results of Dans et al. (14) in Supplementary Figure S6. The results are: (i) strongly non-Gaussian distributions do not arise at all in RY steps, and are restricted to shift for GG steps, slide for all RR steps, and twist for all RR and YR steps. The other three inter-BP, as well as all intra-BP, parameters do not significantly deviate from Gaussian behavior in any sequence context; (ii) only GG slide and CG twist show clear multiple peaks. We remark that while our analysis has identified tetranucleotide fragments whose central base pair steps interconvert between multiple conformational substates, it certainly does not rule out the possibility that other fragments can also have multiple substates, but with populations that are difficult to distinguish using only helical parameter distributions.


μABC: a systematic microsecond molecular dynamics study of tetranucleotide sequence effects in B-DNA.

Pasi M, Maddocks JH, Beveridge D, Bishop TC, Case DA, Cheatham T, Dans PD, Jayaram B, Lankas F, Laughton C, Mitchell J, Osman R, Orozco M, Pérez A, Petkevičiūtė D, Spackova N, Sponer J, Zakrzewska K, Lavery R - Nucleic Acids Res. (2014)

Non-Gaussian and multi-peaked helical parameter distributions. (a) Probability distributions of the inter-BP parameters for the central base pair step of the 136 distinct tetranucleotide sequences were inspected for visible deviations from Gaussian behavior. Helical parameters classed as ‘Multi-peaked’ (red) have two distinct peaks in their distributions for most flanking sequences. Monomodal distributions with obvious deviations from normality (such as pronounced shoulders or asymmetry) for most flanking sequences are classed as ‘Non-Gaussian’ (orange). The results are grouped on the basis of the purine/pyrimidine family of the dinucleotide step. Examples of parameter distributions (see also Figure 3) are shown for the twist of AGCA ((b), multi-peaked) and the shift of TGGT ((c), non-Gaussian).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231739&req=5

Figure 4: Non-Gaussian and multi-peaked helical parameter distributions. (a) Probability distributions of the inter-BP parameters for the central base pair step of the 136 distinct tetranucleotide sequences were inspected for visible deviations from Gaussian behavior. Helical parameters classed as ‘Multi-peaked’ (red) have two distinct peaks in their distributions for most flanking sequences. Monomodal distributions with obvious deviations from normality (such as pronounced shoulders or asymmetry) for most flanking sequences are classed as ‘Non-Gaussian’ (orange). The results are grouped on the basis of the purine/pyrimidine family of the dinucleotide step. Examples of parameter distributions (see also Figure 3) are shown for the twist of AGCA ((b), multi-peaked) and the shift of TGGT ((c), non-Gaussian).
Mentions: The conclusions of our analysis are summarized in Figure 4 and can be compared with the results of Dans et al. (14) in Supplementary Figure S6. The results are: (i) strongly non-Gaussian distributions do not arise at all in RY steps, and are restricted to shift for GG steps, slide for all RR steps, and twist for all RR and YR steps. The other three inter-BP, as well as all intra-BP, parameters do not significantly deviate from Gaussian behavior in any sequence context; (ii) only GG slide and CG twist show clear multiple peaks. We remark that while our analysis has identified tetranucleotide fragments whose central base pair steps interconvert between multiple conformational substates, it certainly does not rule out the possibility that other fragments can also have multiple substates, but with populations that are difficult to distinguish using only helical parameter distributions.

Bottom Line: We demonstrate that the resulting trajectories have extensively sampled the conformational space accessible to B-DNA at room temperature.We confirm that base sequence effects depend strongly not only on the specific base pair step, but also on the specific base pairs that flank each step.By analyzing the conformation of the phosphodiester backbones, it is possible to understand for which sequences these substates will arise, and what impact they will have on specific helical parameters.

View Article: PubMed Central - PubMed

Affiliation: Section de Mathématiques, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.

Show MeSH
Related in: MedlinePlus