DNA Conformations results in different forms of DNA. These conformartions actually arise due to twists and displacement at different positions and torsion angles.

Table of Contents

• Sugar Puckering (DNA conformations)
• Torsions at α, γ and χ
• Helical Parameters
  • Helical parameters
  • Base pair parameter
  • Step parameters
• Grooves
• Topology of DNA

Sugar Puckering (DNA conformations)

• Ribose rings undergoes sugar puckering and become slightly nonplanar.
• Most structures shows that four of the five ring atoms are coplanar, 5^th atom is out of the plane in a half-chair conformation. This results in two conformation.

1. Endo- conformation→ if out of plane atom is the same side of the ring as the C5′ or movement of carbon atom closer to oxygen.
2. Exo- conformation → if out of plane atom is on the opposite side of the ring as the C5′ or movement of carbon atom away from oxygen.

There are four conformations that the ribofuranose rings in nucleotides can acquire:-

1. C-2′ endo
2. C-2′ exo
3. C-3′ endo
4. C-3′ exo

Most nucleoside and nucleotide structures (not in double helices) out of plane atom is either C2′ or C3′. C2′-endo most common; C3′-endo and C3′-exo are also common.

• Ribose is usually in C-3’endo, while deoxyribose is usually in the C-2′ endo sugar pucker conformation.
• The A and B forms differ mainly in their sugar pucker. In the A form, the C3′ configuration is above the sugar ring, whilst the C2′ configuration is below it. Thus, the A form is described as “C3′-endo”.
• Likewise, in the B form, the C2′ configuration is above the sugar ring, whilst C3′ is below; this is called “C2′-endo.”
• Altered sugar puckering in A-DNA results in shortening the distance between adjacent phosphates by around one angstrom. This gives 11 to 12 base pairs to each helix in the DNA strand, instead of 10.5 in B-DNA.
• Sugar pucker gives uniform ribbon shape to DNA conformations, a cylindrical open core, and also a deep major groove more narrow and pronounced that grooves found in B-DNA.

This ribose pucker determines the relative orientation of the phosphates to the sugar.

• To have a regularly repeating model-need C2′-endo (B-DNA) or C3′-endo (A-DNA, RNA-11)
• Z-DNA purines are all C3′-endo, pyrimidines C2′-endo (dinucleotide repeating unit).
• B-DNA has some flexibility (can be observed as C4′-exo, O4′-endo, C1′-exo and C3′-exo).

Torsions at α, γ and χ

• Rotations around α & γ torsions leads to reduced twist and plays important role in the formation of several protein-DNA complexes (figure below).

• Angle χ (chi), defines the glycosyl  bond. Relative to the sugar moiety, the base can adopt two main orientations in DNA conformations about the C1′-N link, called either syn or anti.

• In the anti configuration, the bulky part of the base is pointing away from the sugar (the six membered ring is pointed away from the sugar). For the pyrimidines the O₂ on the C₂ carbon is the bulky group; in anti, this group points away from the base.
• Both Guanine and cytosine as a single nucleotide and in the alternating co-polymer G-C-G-C-G is in the syn configuration. This is probably due to the H-bonding of the N₂ amino group of the guanine to its 5’phosphate.

Important Note:

• Purine residues have two sterically allowed orientations relative to the ribose group, syn- and anti DNA conformations.
• For pyrimidines only the anti conformation is allowed due to steric hindrance between the sugar and the C2 of the pyrimidine.
• Most double helical nucleic acids are in the anti- DNA conformations.
• Exception is Z-DNA which has alternating anti and syn- pyrimidine and purine residues.

Helical Parameters

If a base or base-pairs are taken as a block, six parameters are required to describe the position and orientation of one base-pair relative to another. There are almost three sets of local parameters commonly in use in nucleic acid conformational analysis

Helical parameters

Helical parameters demonstrate the position and orientation of a base-pair relative to the helical axis, defined here by the repetitive of a two-base-pair unit.

• X-displacement ->Translation around the X-axis
• Y-displacement ->Translation around the Y-axis
• Inclination -> Rotation around the X-axis
• Tip -> Rotation around the Y-axis
• Helical twist
• Helical rise

Base pair parameter

Translational (Shear, Stretch, Stagger) and rotational (Buckle, Propeller, Opening) parameters related to a dinucleotide Intra-Base Pair.

• Shear: Translation around the X-axis.
• Stretch: Translation around the Y-axis.
• Stagger: Translation around the Z-axis.
• Buckle: Rotation around the X-axis.
• Propeller: Rotation around the Y-axis.
• Opening: Rotation around the Z-axis.

Are base pairs planar?

The base pairs in nucleic acid structures are not really planar. For example, the propeller twist of AT base pairs in B-DNA is usually in the range of -15° to -20°. If the base pairs are not planar, the six inter base pair parameters will give only a rough model of the helix.

Step parameters

(Shift, Slide, Rise, Tilt, Roll and Twist) which show the stacking geometry between neighboring base-pairs (dinucleotide Inter-Base Pair).

• Shift: Translation around the X-axis.
• Slide: Translation around the Y-axis.
• Rise: Translation around the Z-axis.
• Tilt: Rotation around the X-axis.
• Roll: Rotation around the Y-axis. Twist: Rotation around the Z-axis

These three sets of parameters are obviously interrelated: from one set, the other can be deduced and vice versa. The values of local vs. helical rise and twist from these two sets of parameters can be quite different in DNAs which deviate significantly from B-DNA.

Grooves

Nucleic Acid Structure’s strand backbones appear closer together on one side of the helix than on the other. This creates a major groove (where backbones are far apart) and a Minor groove (where backbones are close together). Depth and width of these grooves can be measured giving information about the different DNA conformations that the nucleic acid structure can achieve. Major Groove Width, Major Groove Depth, Minor Groove Width, Minor Groove Depth

Why are there a minor groove and a major groove?

It is a simple result of the geometry of the base pair. The angle at which the two sugars protrude from the base pairs (that is, the angle between the glycosidic bonds) is about 120° (for the narrow angle or 240° for the wide angle). As a result, as more and more base pairs stack on top of each other, the narrow angle between the sugars on one edge of the base pairs generates a minor groove and the large angle on the other edge generates a major groove. (If the sugars pointed away from each other in a straight line, that is, at an angle of 180°, then two grooves would be of equal dimensions and there would be no minor and major grooves).

Topology of DNA

• Metabolic events like replication transcription that involves unwinding of DNA results in great stress on the DNA because of the constraints inherent in the double helix, hence can change DNA conformations.
• Their are enzymes are called DNA topoisomerases. In addition to the requirement to unwind DNA for replication and for transcription, there is an absolute requirement for the correct topological tension in the DNA (super-helical density) in order for genes to be regulated and expressed normally.
• DNA that is underwound is referred to as negatively supercoiled. DNA that is overwound also will relax and assume a supercoiled conformation but this is referred to as a positively supercoiled DNA helix.

Linking, Twisting and Writhing (DNA conformations)

• The number of times one strand of the DNA helix is wind/linked with the other helix in a covalently closed circular DNA molecule (cccDNA) is known as the linking number L_k.
• The value of linking number L_k is fixed or does not change as long as the the DNA molecule remains covalently closed.
• The value of linking number L_k of a circular DNA can only be changed by breaking a phosphodiester bond in one of the two strands which then allows the one strand to pass through the broken strand and then rejoining the broken strand.
• The value of linking number L_k is always an integer.
• The linking number of a covalently closed circular DNA can be resolved into two components called the twists T_w and the writhes W_r.

Lk = Tw + Wr

The twists T_w are the number of times that the two strands are twisted about each other.

Writhes W_r is the number of times that the DNA helix is coiled about itself in three-dimensional space.

The twist and the writhe are not necessarily integers;

Suppose, there is a DNA molecule which is of 5243 base pairs in length, we would find that:

Lk= T_w + W_r

480 = 5243/10.4 – 24.13

480 = 504.13 – 24.13

[Tw = Length (bp)/Pitch (bp/turn)]

The twist and the linking number, determine the value of the writhe that forces the DNA to assume a contorted path is space. [W_r = L_k – T_w ].

Let us illustrate supercoiling with a simple example as follows.Suppaose, a relaxed DNA circle with a 1000 bp. We assume that there are 10 bp per every turn of DNA. Or this molecule contains a 100 turns, or its Lk₀ = 100.

Lk = Tw + Wr;

In our relaxed molecule, Wr = 0.

Lk₀ = 100 = T_w + 0

Let us remove 20 turns from this molecule by breaking a strand and resealing it. Now there are only 80 turns in this molecule, or L_k = 80.

L_k = 80 = T_w + W_r.

If we force the axis to be planar, thus keeping W_r = 0,

80 = Tw +0

The twist is now 80, and therefore the pitch of the helix changes, it is no longer 10 bp per turn, rather 1000/80 or 12.5 bp per turn.

Now, let us keep the twist the same (100 turns; 10 bp per turn), and partition the negative supercoiling entirely into writhe.

L_k = 80 = 100 + W_r

W_r = 80 – 100 = -20

Or the axis coils over itself 20 times. This is negative supercoiling and these negative supercoil nodes are minus .

If you do the above exercise by adding 20 turns, you get positive supercoiling, and the signs of the supercoil nodes will be positive.

Linking difference (Δ Lk): The change in the linking number, ΔLk, is the actual number of turns in the plasmid/molecule, Lk, minus the number of turns in the relaxed plasmid/molecule Lko.

Lk=Lk-Lko

If the DNA is negatively supercoiled ΔLk < 0. The negative supercoiling implies that the DNA is underwound.

Superhelical density (σ): A standard expression independent of the molecule size is the “specific linking difference” or “superhelical density” denoted σ, that represents the number of turns added or removed relative to the total number of turns in the relaxed molecule/plasmid, indicating the level of supercoiling in DNA conformations.

σ = ΔLk/Lko