Let’s look more closely at the building blocks of DNA – the nucleotides.

Notice that it is more complex than an amino acid, where three complex chemical groups are covalently linked together. And unlike amino acids, nucleotides are not recovered in Miller-Urey type experiments. In fact, Robert Shapiro, professor emeritus of chemistry and senior research scientist at New York University, notes:

And no sample of a nucleotide, the building block of RNA or DNA, has ever been discovered in a natural source apart from Earth life. Or even take off the phosphate, one of the three parts, and no nucleoside has ever been put together. Nature has no inclination whatsoever to build nucleosides or nucleotides that we can detect, and the pharmaceutical industry has discovered this.

What is also remarkable about nucleotides is that it is possible to connect the sugar, phosphate group, and nitrogenous base together to form different structures.

In their book, The Mystery of Life’s Origins, Thaxton et al. calculate there are 45 different isomers of the above nucleotide. And when it comes to forming a dinucleotide, shown in the figure below, Thaxton et al. calculate 720 different ways of connecting things together.

Yet life only uses the particualr arrangements as shown in the above figures.

This particular “arbitrary” arrangement that is not readily produced by Nature has a remarkable implication when it comes to forming the double helix and the pairing of bases on opposite strands. Once again, let’s look down the double helix, where we can see one base pair highlighted in white.

As a consequence of the asymmetric arrangement of groups in the two nucleotides, note that the distance from one edge of the double helix to the other edge is greater just above the base pairs than it is just below the base pairs. It might be easier to see this if we just focused on one base pair, as in the figure below

Note that the greater distance is called the “major groove face.” Because the two strands of DNA wind around each other, we can think of these base pairs as rotating as we move downward. This means that the double helix will have asymmetrical grooves on opposite sides – a wider one known as the major groove and a more narrow one known as the minor groove.

We cannot see the grooves by looking down the axis of the DNA but we can see them when looking at DNA along it’s length as seen in the figures below.

All of this means is that the sequence of nitrogenous bases are more accessible in the major groove. In fact, there are very common DNA-binding protein motifs known as zinc fingers, leucine zippers, and helix-turn-helix that bind to the DNA by “touching” the bases within the major groove.

So let us now turn to the proteins. There are two basic rudimentary folds that occur – the alpha helix and the beta sheet. Let’s focus on the alpha helix since it is the fold from the various DNA binding proteins listed above that binds the major groove . A figure of an alpha helix is shown below:

This helical structure is stabilized by hydrogen bonds (the dotted lines) between the C=O group of one amino acid and the N-H group of the amino acid four subunits downstream (as more easily seen in the figure below):

There are a few things to note about the alpha helix. Although side chain identity can influence whether or not an alpha helix is formed, it forms largely by the same groups that are involved in the peptide bond. Second, short peptides do not normally form alpha helices, which means this is a fold that will effectively emerge from larger chains of amino acids. Third, note that the side chains extend outward from the helix, in contrast to the way the nitrogenous bases point inward in the DNA helix. Below shows a figure where the outward pointing side chains (in green) are more easily seen (especially c and d):

Thus, as a consequence of amino acid structure, proteins will not only form folded structures using the same rules that form the double helix of DNA, , but they will form a cylindrical structure whose appendage (side chains) seem to be well-matched for scanning and binding to the winding major groove along the double helix. That is, the pattern of outreaching side chains can reach into the major groove and interact with the pattern of base-pairs inside the wide crevice of the major groove. But how well matched is the alpha helix and major groove?

According to this article:

alpha helices have particular significance in DNA binding motifs, including helix-turn-helix motifs, leucine zipper motifs and zinc finger motifs. This is because of the structural coincidence of the alpha helix diameter of 12Å being the same as the width of the major groove in B-form DNA.

Why think it is merely a coincidence that the alpha helix diameter and the width of the major groove are the same? On the contary, it simply enhances and extends the inheret rationality and complementarity that lies behind these two crucial biological molecules – a match made in heaven.

There’s more to mine here, but I think I will take a break from proteins and DNA for the time being.