That’s Random! A Look at Viral Self-Assembly

| By Kathryn Applegate on Endless Forms Most Beautiful

Originally posted April 8, 2010.

That’s Random!  A Look at Viral Self-Assembly

You hear it all the time: “That’s so random!” When used by people of my generation, the word “random” can simply mean “cool” or “surprising.” Or it can mean something like “disconnected,” as in the phrase, “I had a random thought” (which returns 189,000 hits on Google, by the way—random!).

Despite this usage, most of us know that randomness has something to do with probability, and that it often implies a lack of conscious intentionality. But what do mathematicians and scientists mean when they say something is random? Can a random process lead to an ordered, even predictable outcome? Is there evidence that God makes use of random processes to fulfill his creative purposes?

These are big questions, and we won’t address them all today. But I think randomness is an important topic to cover for two reasons: 1) it is integral to many processes in biology (and math, physics, chemistry, etc.), and 2) it is commonly misunderstood to be incompatible with Christianity.

As I said above, most of us know that randomness has something to do with probability. If you pick a card “at random” from a shuffled deck, you have a small probability of drawing an ace (4 out of 52, or a 7.7% chance). If you flip a coin, you have an equal probability of getting heads or tails.

Randomness also seems to imply a lack of intentionality or purposefulness. After all, you might hope for an ace when you draw a card, but you can’t choose one on purpose. You might call heads when you flip a coin, but you can’t know beforehand what the outcome will be. Thus the outcome is indeterminate, but is it purposeless? Not necessarily. Indeterminacy simply means the result cannot be predicted from the outset.

It should be noted that indeterminacy does not imply that God does not have foreknowledge of future events. Christians ought not to be uncomfortable with the idea of God interacting with his creation through chance. We often describe a seemingly-random (i.e. unplanned by us) sequence of events as being “providential,” or planned by God.

In biology, it is very hard or impossible to calculate precise probabilities for most processes, so when we say a process is random, we typically mean it is extremely unpredictable. Eventually we will discuss randomness within biological evolution, but first we must consider some simpler processes, like the self-assembly of a virus.

Viruses are remarkably efficient entities. Coiled tightly within a protein-based shell is a small amount of DNA needed for self-replication. The shell, called a capsid, is made of many repeating protein subunits and is therefore highly symmetrical (see figure). Important biomedical insights have certainly been gleaned from structural studies of viruses, but viruses also teach us about the emergence of order from non-order.

The virus life cycle has four main steps: 1) enter a host cell, 2) hijack the cell’s replication and translation machinery to make many copies of itself, 3) assemble into many virus particles, and 4) exit the cell to invade another host.

When I first learned about this process, I found it very hard to believe it just “happens.” The idea that a bunch of molecules bumping into each other inside a crowded cell could spontaneously assembly into a fully-functional virus seemed a bit far-fetched. Many viral capsids have over 100 protein subunits that must interact with each other in just the right way, or it won’t work. Surely there must be something driving this process, right?

There is! Random motion. I had to see it to believe it. I distinctly remember sitting in class during my first year of graduate school when the professor demonstrated self-assembly of a virus using a 3D model as shown in the following video. In less than 30 seconds, you can watch a jumbled heap of proteins become a beautifully ordered structure.

As the narrator explains, sub-assemblies form and break apart en route to the most stable structure, the full capsid. As the sub-assemblies begin to form, further associations with free subunits become more favorable and as a result occur rapidly, while the final steps may take considerably longer. While the subunits in the model are rigid, in reality the proteins take on multiple conformations, allowing the capsid to “breathe.”

Amazing as it is, the system we just considered—one virus capsid in a jar—is pretty simple. One wonders how self-assembly can happen in a crowded cell, where there are countless other molecules diffusing around, potentially getting in the way. We can’t directly see how it happens in a cell, but we can reconstitute the process in a test tube using different combinations of constituent molecules.

Consider two viruses, where each protein subunit in one virus is the mirror image of the corresponding subunit in the other. Putting the two viruses together by hand would be pretty tricky, because the constituent parts look so similar. But random motion can do the job in short order:

From this model, we can see clearly, in real-time, how distinct complex structures can arise from their parts randomly interacting with one another. Many large viruses also use special scaffolding proteins to assist in the assembly process, and some even use their own genomes as a scaffold. In addition, two closely-related viruses that happen to infect the same cell can exchange parts to create a new virus. This is one way viruses can evolve quickly to evade the host’s immune system.

Here we have seen how viruses demonstrate a principle inherent in God’s world—that order can emerge out of chaos from random processes. In my next post, we will look at some other biological processes that make use of—rather, depend on—randomness. This will set the stage for us to see that such processes can not only assemble a structure within seconds or minutes, but also generate complex, information-bearing molecules over billions of years. Even though the freedom inherent in nature sometimes produces unintelligently-designed structures (like viruses, which can kill us), we see that God has made, and continues to oversee by his providence, a good creation that, at least in part, is capable of creating itself.

We’ll continue this series about randomness and God’s divine will. Up next: how God created the body to heal itself, and how can random mutations can be both harmful and benign.


About the Author

Kathryn Applegate

Kathryn Applegate is Program Director at BioLogos. She received her PhD in computational cell biology at The Scripps Research Institute in La Jolla, Calif. At Scripps, she developed computer vision software tools for analyzing the cell's infrastructure, the cytoskeleton. 


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