Understanding the Flexibility of the Sugar-phosphate Backbone

Although the bases of the nucleic acids are insoluble in water, this is no longer a problem once they are attached to a pentose sugar and a phosphate to become a nucleotide. However, the hydrophobic face of the bases does place strong constraints on the overall conformation of a large DNA or RNA molecule in solution. The sugar-phosphate backbone of the polynucleotide also imposes strong constraints on the overall conformation of the chains, whether we are discussing single- or double-stranded DNA.

The Phosphate Groups Acts as a Swivel

It is the flexibility of the sugar-phosphate backbone that allows two antiparallel strands of DNA to form a double helix. This flexibility arises in large part from the phosphates in the backbone. The phosphate group itself is a rigid tetrahedron, having a phosphorus atom at its center and one oxygen at each vertex. Only when we attach two carbons to two of the oxygens, can these carbons rotate around the phosphorus-oxgen bonds, as shown by the yellow bonds in JSmol.

Imagine that your shoulder is the phosphorus, your elbow is the oxygen, and your hand is one of the carbons. Obviously you can rotate your forearm and hand relative to your shoulder but in DNA the P–O–C bond angle is fixed, whereas the angle of your arm relative to your shoulder is not. Each yellow bond in JSmol indicates the possibility of rotation around a bond. Close your fist, stick your thumb out, and then rotate your forearm. Just as your thumb will point in different directions, so will rotation around the O–C bond change the direction of the nucleotide chain. However, we know that the situation is not as simple as this and that the carbon atoms in the phosphodiester are restricted in the directions they can assume by steric constraints.

Constraints on the Backbone

The relative orientations of the backbone are described by rotations around each bond. That seven parameters are needed to describe the conformation of a nucleotide unit gives you some idea of the flexibility in the sugar-phosphate chain of the nucleic acids. These parameters, called torsion angles, are represented by the yellow bonds. Free rotations around these bonds would, in principle, allow the chain to adopt a very large number of conformations. Again, we know that the situation is not that simple and that steric clashes between atoms will exclude most conformations. Therefore, in solution the chain will spend most of the time in a relatively small number of conformations.

Flexibility of Nucleotide Units

Functions of nucleic acids depend not only on their structure and stability, but also on their dynamics. To illustrate the flexibility of the sugar-phosphate backbone, let's look at all allowed conformations of a nucleotide unit. The model shows two carbon atoms linked to the phosphate groups at each end of the nucleotide unit in order to show different conformations of a phosphodiester linkage.

Toggle spacefill. Because we know that any atom in a molecule cannot occupy a space already occupied by another, only space-filling gives you a feeling for the limited conformational space of the sugar-phosphate chain.

This structure, generated by NMR, of a small piece of DNA has six backbone torsions. For clarity, the conformation of the adenine base relative to the plane of the ribose is frozen. Watch as the backbone adopts different conformations. In particular, note the range of motion of the carbon atoms at each end.

From the NMR, it is clear that the rigid phosphate groups indeed act as swivels, allowing the sugar-phosphate backbone to twist into different conformations.