Scientists have long known what drives the flagellum to spin, but what causes the flagellum to stop spinning — temporarily or permanently — was unknown.

“We think it’s pretty cool that evolving bacteria and human engineers arrived at a similar solution to the same problem,” said IU Bloomington biologist Daniel Kearns, who led the project. “How do you temporarily stop a motor once it gets going?”

The action of the protein they discovered, EpsE, is very similar to that of a car clutch. In cars, the clutch controls whether a car’s engine is connected to the parts that spin its wheels.

-ScienceDaily (June 23, 2008)

Excerpts from The Design Matrix (2007):

We are actually using the knowledge about our own designed artifacts to shed light on biology and how it works. Imagine if there were no computers, tape recorders, and washing machines. Take away human technology, and suddenly, there are no good metaphors left to describe life. - p 52

All of this, of course, makes sense if life really is carbon-based nanotechnology. To understand an alien technology, we would have to use our own technology as a model, and the more similar the technologies, the more easily we could characterize and understand this alien technology. - p 53

If living processes are the products of design, it comes as no surprise that so much of biology is more akin to the study of engineering than to chemistry or physics. Furthermore, it would make sense that as our understanding of the cell advances, that teleological concepts, including the very concept of design, would proliferate in the biological literature. Much of this design terminology stems from the fact that biologists have discovered that cells are filled with miniature machines and that coded information is stored and employed for the synthesis of these machines.- p. 59

Looking at a cell is like looking into the future of our own designs. – p. 204

Here is a Wordle of Chapter 6 from The Design Martrix:

Below the fold is a Wordle of Chapter 2 and then Chapter 7.

Yet this very example serves to make both points. Yes, evidence is important when making decisions about our natural and social world, but relying solely on the evidence may very well deliver only a superficial, or even false, understanding of the world. We know this simply from the fact that in court rooms around the world, judges and juries have followed the evidence before them to determine guilty people are innocent and innocent people are guilty. This holds true even if we rule out corruption and biases.

Consider some movie where you, the viewer, know that Jones killed Smith, because you watched it happen. Jones, of course, subjectively knows that he killed Smith. The police investigator doesn’t know this, he simply believes that Jones killed Smith because of some clues. The investigator then privately confronts Jones and accuses him of murder. Jones, privately knowing the investigator is correct, simply replies, “There is no evidence and you can’t prove it” and the investigator knows this is true.

Right there, in that scene, we see the difference between evidence and truth. Relying solely on the evidence may very well deliver only a superficial, or even false, understanding of the world.

For example, a simple enzyme protein could be viewed as a computational element that takes an input—the concentration of its “substrate,” the molecule with which it interacts—and produces an output: a concentration of the catalyzed reaction product. An enzyme that becomes active only when it binds to two separate regulator molecules will function something like a Boolean AND gate, and so on. Circuits formed from these elements can be as simple as a switch or an oscillator, or as complex as to drive a bacterium’s chemotaxis response. Indeed, the cell even possesses a kind of short-term, “random-access” memory, in the sense that events in its environment have profoundly shaped the concentration and activity of many thousands of molecules in the cell. In short, these protein-based circuits constitute a kind of nervous system for the cell, providing it with much of what it needs to control its behavior.

Additional insights can be gained from the notion that both computational processes and biological pathways can be viewed as processes that affect the state of a system according to well-defined (though possibly probabilistic) rules. Thus, it is possible to describe regulatory, metabolic, and signaling pathways, as well as multicellular processes such as immune responses, as systems of interacting computations operating in parallel. In particular, languages such as Petrinets, Statecharts, and the Pi-calculus, originally developed for the specification and study of systems of interacting computations, can be used to represent such systems. Such representations enable researchers to simulate their behavior, and to support qualitative and quantitative reasoning on the properties of these systems.

- From
Catalyzing Inquiry at the Interface of Computing and Biology, pp. 207-208

The difference between artificial and natural objects seems immediately and unambiguously apparent to all of us. A rock, a mountain, a river, or a cloud – these are natural objects; a knife a handkerchief, a car – so many artificial objects, artifacts. Analyze these judgments, however, and it will be seen that they are neither immediate nor strictly objective. We know that the knife was man-made for a use its maker visualized beforehand. The object renders in material form the preexistent intention that gave birth to it, and its form is accounted for by the performance expected of it even before it takes shape. It is another story altogether with the river or the rock which we know, or believe, to have been molded by the free play of physical forces to which we cannot attribute any design, any project, or purpose. Not, that is, if we accept the basic premise of the scientific method, to wit, that nature is objective and not projective.

Hence it is through reference to our own activity, conscious and projective, intentional and purposive-it is as makers of artifacts-that we judge of a given object’s “naturalness” or “artificialness.” Might there be objective and general standards for defining the characteristics of artificial objects, products of a conscious purposive activity, as against natural objects, resulting from the gratuitous play of physical forces? To make sure of the complete objectivity of the criteria chosen, it would doubtless be best to ask oneself whether, in putting them to use, a program could be drawn up enabling a computer to distinguish an artifact from a natural object.

Such a program could be applied in the most interesting connections. Let us suppose that a spacecraft is soon to be landed upon Venus or Mars; what more fascinating question than to find out whether our neighboring planets are, or at some earlier period have been, inhabited by intelligent beings capable of projective activity? In order to detect such present or past activity we would have to search for and be able to recognize its products, however radically unlike the fruit of human industry they might be. Wholly ignorant of the nature of such beings and of the projects they might have conceived, our program would have to utilize only very general criteria, solely based upon the examined objects’ structure and form and without any reference to their eventual function.

There are two things to notice about this passage. First, I am struck by the similarities to ID101. I’ll let readers see if they can spot any points of convergence.

Second, and more importantly, this sentence stands out:

Hence it is through reference to our own activity, conscious and projective, intentional and purposive-it is as makers of artifacts-that we judge of a given object’s “naturalness” or “artificialness.”

Maybe it is simply not possible to make such judgments without accessing this subjective element. After all, recognizing design may indeed be akin to recognizing another mind. For how do we recognize other minds if not by recognizing what they design?

This would explain why science has never come up with an objective method for detecting the existence of design.

Instead of assuming it is possible to objectively identify design, let’s instead assume that reference to our own activity, conscious and projective, intentional and purposive- as makers of artifacts-is necessary. And build from there.

If this is the case, then those who have read The Design Matrix can begin to appreciate the methodology I have outlined within. The method I advocate embraces the truth that Monod mentions and builds on it:

The Design Matrix is a method by which you can score a particular feature according to four different criteria to assess and quantify the strength of a design inference. Since detection of design may involve subtleties embedded in complexity and ambiguity, the Design Matrix taps into the most complex and sensitive “instrument” that we can work with to detect such subtleties—the human brain. Since we are by nature designers, we all have a certain awareness of design. The Design Matrix allows one brain’s score to be thoroughly assessed by other brains, perhaps helping us to eventually reach consensus or to better understand why consensus has not been reached. - p. 268

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.

But we have also seen this very logic is at play when it comes to the formation of a chain of nucleotides. As with the side chains of amino acids, the nitrogenous bases can interact with each other through noncovalent forces causing the nucleotide chain to fold into a three-dimensional structure. This is what happens with a lot of RNA and explains its ability to function as a catalyst. But let’s turn to DNA.

With DNA, two nucleotide chains, running in opposite directions, form the well-known double-helix. The thymines on one strand hydrogen bond with the adenines on the other strand, while the guanines hydrogen bond with the cytosines. But it’s more than this. If we look down the end of the DNA double helix, we’d see something similar to the picture shown below.

You can notice one set of base pairs highlighted in white. But as the two strands wind around each other, note how the base pairs stack on each other (the inner circular structure) while the sugar and phosphate groups surround them. This is because the bases are hydrophobic and are thus shielded from the water by the surface sugar/phosphates. And what this means is that it is hydrophobic forces that drive the two strands together, where the hydrogen bonds simply add an additional layer of stabilization coupled to specificity.

The same logic thus applies when forming the double helix of DNA and the folded protein. Both are linear molecules, where a particular sequence is connected together by covalent bonds. Both have appendages that that interact with each other via a pattern of noncovalent forces. Hydrophobic forces collapse a protein into a compact structure and electrostatic forces impart further stability and specificity. Hydrophobic forces drive the double helix together and electrostatic forces impart further stability and specificity. Globular proteins have a hydrophobic core and a hydrophilic surface. The DNA double helix has a hydrophobic core and a hydrophilic surface. And perhaps most remarkable is that Monod’s observation equally applies to both:

The result is that structures defined by noncovalent interactions can attain a certain stability only if they entail multiple interactions. Furthermore, noncovalent interactions acquire a notable amount of energy only when atoms lie a very short distance apart, practically “touching” one another. Consequently two molecules (or areas of molecules) will be able to contract a noncovalent association only if the surfaces of both include complementary sites permitting several atoms of one another to enter into contact with several atoms of the other.

In essence, this is variation on the same logical theme. Same story; different play.

The main differences are twofold: 1.) The pattern of “touching” in the DNA molecule is what codes for the pattern of “touching” in a protein; 2) the sequence of bases on one strand of DNA are complementary to the other strand, meaning the pattern of “touching” in the DNA molecule also “codes” for efficient replication. As I write in The Design Matrix:

The fact that DNA exists as a double helix of two nucleotide chains foreshadows the manner in which the structure of DNA is perfectly suited for replication. To replicate DNA, all you need to do is unwind the two strands and then use each strand as a template for the synthesis of a new, complementary strand. In one molecule, there are two perfect solutions for two design problems—coding the machinery of life and perpetuating the information across time. A more beautiful molecular expression of the form-function relationship would be hard to imagine. Seen from this vantage point, the very structure of DNA is evidence that indicates life was designed to reproduce.

The differences thus complement the similarities and become one.
But what happens when the protein theme meets the DNA theme? What happens when the proteins “touch” the DNA?

What I’d like to do now is impress upon you the very brilliance of this design, as it goes a very long way in explaining why proteins have been so useful for evolution.

What you have here is a strategy that links subunits by covalent bonds, but the folding, and thus function, is determined by forces much weaker than covalent bonds.

As Joachim Pietzsch notes,

the folding of a protein is not a chemical reaction, with a bond breaking here and a new one forming there. It is more like the weaving of an intertwined molecular pattern, the stability of which is defined by innumerable forces between atoms.

In his classic book, Chance and Necessity, Jacques Monod explores the implications in more detail as he explores the difference in activation energy when forming covalent bonds and noncovalent bonds:

Simplifying somewhat, and specifying that we are now considering only those reactions occurring in aqueous phase, we may say that the average amount of energy absorbed or liberated by a reaction involving covalent bonds is on the order of 5 to 20 Kcal per bond. For a reaction involving noncovalent bonds only, the average amount of energy would be between 1 and 2 Kcal.

This considerable difference partially accounts for the difference in stability between covalent and noncovalent chemical constructs. The essential, however, lies not there but in the differences in the so-called activation energies brought into play in the two types of interactions.

[….]

Now- and this is the crucial point – in general:

a. The activation energy of covalent reactions is high; their speed is therefore very slow or zero at low temperatures and in the absence of catalysts; while

b. The activation energy of noncovalent reactions is very low if not zero; they therefore occur spontaneously and very rapidly, at low temperature, and in the absence of catalysts.

The result is that structures defined by noncovalent interactions can attain a certain stability only if they entail multiple interactions. Furthermore, noncovalent interactions acquire a notable amount of energy only when atoms lie a very short distance apart, practically “touching” one another. Consequently two molecules (or areas of molecules) will be able to contract a noncovalent association only if the surfaces of both include complementary sites permitting several atoms of one another to enter into contact with several atoms of the other.

If we now add that the complexes formed between enzyme and substrate are of noncovalent nature it will be seen why these complexes are necessarily stereospecific: they can form only if the enzyme molecule has a site “complementary” to the shape of the substrate molecule.

So what does all this mean? We link amino acids together in a process that will depend on catalysts (explaining why proteins depend on the molecular machine known as the ribosome for their origin). This speaks to stability. But what is stably linked together? A pattern of side chains that has the potential to spontaneously adopt a three-dimensional shape that is, in essence, programmed by the sequence. The one-dimensional “virtual world” codes for the emergence of a three-dimensional world, where form becomes function. And it does so in a way that imparts both specificity (the need for multiple interactions) without determinism (the whole system is dynamic, thus flexible, thus responsive). With building material like this, the blind watchmaker could not help but be a success!

But let’s next turn back to DNA, the other biological molecule that shares some rather deep conceptual similarities with proteins. Could proteins and DNA be “a match made in heaven?”

I’d like to draw your attention to two things. First, note that the carboxyl group of one amino acid reacts with the amino group of the second amino acid to form the peptide bond (highlighted in the orange box). This creates a dipeptide with differing ends. At the N-terminal end, there is a free amino group and the C-terminal end has a free carboxyl group. This simply means we can attached a third amino acid to the C-terminal end of the dipeptide with the very same reaction. And if we can add a third, we can add a fourth. Etc. Thus, the structure of the amino acid is perfectly poised to create a growing chain whose length would be determined by factors other than amino acid structure. We can thus begin to catch a glimpse of one reason why proteins are so versatile, as the relative ease of construction is coupled to an ability to vary the length.

But let us now consider something that is even more interesting. Notice the two R groups, R1 and R2. These represent the side chains of each respective amino acid that we briefly discussed in the previous essay. What you should notice is that side chains do not participate in the linking of amino acids. On the contrary, they simply stick out as appendages on the backbone chain of amino and carboxyl groups. And because they do not participate in this linkage, it means that the sequence of side chains is not chemically determined by the process of polymerization. In essence, it is programmable.

These exact same themes are represented in nucleic acids, RNA and DNA. In these cases, the building blocks are more complex and known as nucleotides.

Above is a figure of a nucleotide, showing its three parts: the pentose sugar, a phosphate group, and the nitrogenous base. The nitrogenous base is the analog of the amino acid’s side chain, only this time there are four types: uracil (U), guanine (G), cytosine (C), and adenine (A) in RNA and thymine (T), guanine (G), cytosine (C), and adenine (A) in DNA.

The nucleotides are linked together into a chain through interactions between the phosphate group of one nucleotide and the sugar of an adjacent nucleotide. We’ll call this covalent bond the sugar-phosphate bond and the resulting chain is shown in the following figure:

Notice that as with proteins, the ends are different. The top end contains a free phosphate group and is called the 5’ end (because that phosphate group is bonded to the 5’ carbon of the sugar). The bottom end with the exposed sugar is called the 3’ end. To grow the strand, we need to attach a fourth nucleotide to the 3’ end. Thus, the structure of the more complex nucleotide is perfectly poised to create a growing chain whose length would be determined by factors other than nucleotide structure.

But notice also the way the nitrogenous bases mimic the R groups of amino acids: they do not participate in the formation of the sugar-phosphate bond. On the contrary, they simply stick out as appendages on the sugar-phosphate backbone. And because they do not participate in this linkage, it means that the sequence of nitrogenous bases is not chemically determined by the process of polymerization. In essence, it is programmable.

Thus, what we have is a profound conceptual similarity between two unrelated molecules. It is this similarity in basic format that will allow the nucleic acids to encode the amino acid sequence of a protein.

In the next essay, we’ll see how the similarities begin to diverge only to reunite in a most remarkable manner.