Predicting Protein Functions from Primary Structure -- a 20 yr old idea of mine

Once upon a time, in the early 1990's, I was in graduate school studying molecular biology. I developed a thesis project, which I never pursued and which, to my knowledge, no one has ever pursued.

The project would have been one of the first forays into bioinformatics. The idea was to use an artificial neural net (ANN) to predict protein function from primary structure. Basically, one would create inputs of known proteins' amino acid sequences and the qualities of each of those amino acids, including whether they were:

1. Polar / hydrophilic
2. Non-polar / hydrophobic
3. H-bonding
4. Sulfur containing
5. Charged at Neutral pH Negative / acidic
6. Charged at Neutral pH Positive / basic
7. Ionizable
8. Aromatic (and potentially stacking)
9. Aliphatic
10. Forms covalent cross-link (disulfide bond)
11. Cyclic
12. C-Beta branching
13. pK values
14. pI values
15. Ka values

One might also use secondary and tertiary structures when known as inputs. This would certainly contribute to more accurate outputs.

The outputs of the ANN would of course be the protein function, though it is perhaps not impossible that some structural predictions -- of alpha helices or beta sheets, for example -- could not be an output for such a system.

As for discovering the best ANN architecture, perhaps genetic algorithms could be used. There is no telling what is the optimal architecture, so some sort of evolution and selection process would likely be most efficient.

Of course, it may  be possible that there are programs other than ANNs that could do this better/more efficiently. I suggest ANNs because they are able to conceptualize and therefore make pattern predictions, which is what a program like this, with the outputs desired, require.

If anyone thinks this worth pursuing, I encourage you to do so. I just ask for a courtesy 10% of any profits. :-)

Leiter's Theocracy

Brian Leiter is right. Rule of law means equality under the law, meaning there should not be special exceptions and exemptions for any given group. This includes religion.

But that point is as far as Leiter is right. And he is right that America is not a theocracy. And that last point he makes is why he could not be more wrong in the rest of his piece.

If rule of law means no one can be exempt, then if there is a case where law violates someone's religious liberty (which I do believe is law in this country), then that means the law itself should not be in place, as it inherently violates the rule of law. Any law that forces someone to choose between it and their conscience is no law.

Now, we are not talking about those laws that are protective in nature. You should not be allowed to murder, rape, steal, or assault in the name of God(s). What we are talking about are those laws that are not inherently protective in nature, but simply reflect someone's particular moral code. That would include laws against drugs and prostitution, many of the provisions in the ACA -- in fact, many of the laws currently on the books. Each of those laws are expressions of some group or groups' moral code. It is thus fundamentally theocratic, since the point of theocracy is to impose one particular moral code (God's, of course) on everyone. Thus, every single example Leiter gave is a theocratic law intended to impose one set of morals on everyone else, even those who do not subscribe to that religion.

A great example of this is the law against polygamy, which members of other Christian religions imposed on Mormons through the power of the federal government. The impetus behind prohibiting polygamy was purely religious, and was used to violate the consciences of those in another religion. If Leiter wants a good example of theocracy, that law would be it.

In fact, if we do not want a theocratic government, we would get rid of all laws that violate the consciences of all religious believers, and do not impose any one religion's views on the rest. That would in fact be rule of law -- not what Leiter supports, which is the establishment of his own theocracy.

Evolution in Music, Genes, and Language

Music seems to coevolve with genes, whereas language evolves more quickly. Which only makes me wonder about how this affects the evolution of songs and poetry. Might this more ancientness of music be one of the things that stranges language when it's made more musical?

And why does music evolve more slowly, at the rate of genes? Might it be because music is so much more connected to our emotions, which equally evolve at a glacial pace? Language is liberated from pure emotivity, able to express in logical structures as well. And sentiments give rise to emotions and moral responses equally, suggesting music (and language) are connected to sentiments. Logos, pathos. ethos.

And music, then, brings language back to being more sentimental -- expressing emotions and moral content more strongly, bringing them back in balance with the logical content of language. And yet, one cannot escape the logic and reason inherent in language, even in poetry.

The Secret of Educational Reform

My latest at The Pope Center is The Secret of Educational Reform.

Is it top-down reform? No. Impossible to do.

Is it argumentation? No. People are in fact practically unpersuadable.

Then what is it? Hint: how do you create empathy and persuade unconsciously?

Moral Layers in Literature

As the evidence rolls in that literature has an effect on an individual's moral development simply through the act of reading, we need to remind ourselves that literature also has a content, and authors, and that one cannot escape the fact that each contribute a moral element as well.

While it is true that just the act of reading literature makes us more empathetic, improves our theory of mind, and complexifies our minds, but works of literature have authors of varying morals and content of equally varying morals (with many in the 20th century varying toward the immoral). Despite declarations of the death of the author, we remain interested in them. And surely (author-created) content has an effect on readers.

Certainly it does. And it does so on several levels.

Since we started with the broadest discussion of literature qua literature and the effect on our improved empathy, let us start broad and consider the sense of life of given genres and works.

Reading tragedies allow us to understand and perhaps develop a tragic sense of life. What is the tragic sense of life? It is a realization that everything you do has unintended consequences, that the smallest things can have the biggest effects. The more Oedipus runs away, the closer he gets to his destiny. An accidentally dropped handkerchief leads to the murder of Desdemona at the hands of her husband, Othello. A conflict between duties for Orestes (one must avenge one's father's death; one must never murder one's own parents) results in the establishment of the Athenian system of justice through trial by jury. Those who deny life is tragic want to condemn the past, cut society from it, and recreate it in their own image. The results would be comic if it weren't for the lives ruined and even lost in such efforts.

Reading comedies allow us to develop our specific moral sense -- but does so at the expense of others (though sometimes at our own expense, in self-deprecating humor). It in many ways reinforces the Us-Them dichotomy, but does so along moral lines. Comedy invites us to laugh at our own shortcomings -- often moral, but sometimes perceptual and/or cognitive (as in the case of mistaken identity in twins in a variety of plays, including the Amphitryons of both Plautus and Moliere, and Shakespeare's The Comedy of Errors) -- as well as the shortcomings of others (which may have turned out to be our own without the lessons of comedy).

Romanticism, realism, neoclassicism, naturalism, existentialism -- all are going to have an effect on our world views and sense of life, and thus affect our morals. To find joy in things, or sorrow in them -- each affects our moral development. The more things we find beautiful, the more moral we become -- for virtue aims at the beautiful (Aristotle). And insofar as art shows us truths we may not have understood before, the more moral we are -- for beauty is truth, truth beauty (Keats), meaning virtue aims at truth. This may then equally suggest that artistic efforts to undermine our sense of beauty equally undermine our morals. The less beauty there is in the world, the fewer things at which we can aim, and the more restricted our moral spheres will become.

But these are all broad senses in which literature can affect our moral development. What about specific content? Is not Nabakov's Lolita an immoral tale of an immoral narrator? And if we grant the incredible artistic merit of Lolita, surely there is nothing but moral repugnance in the world of the Marquis de Sade. The moral atrocities in Philosophy in the Bedroom are seemingly endless. Though we do get the words "sadism" and "sadistic" from Sade's name, it doesn't seem that we saw an actual increase in sadistic behavior since the publication of Sade's works. In fact, Gad Saad points out in The Consuming Instinct that exposure to pornography does not result in an increase in rape, promiscuity, cheating, or misogyny; it rather has the opposite effect. Perhaps through a kind of cathartic effect, or perhaps through a kind of passive Freudian bringing-to-the-surface of the contents of one's id in the safe dream/play space of the work of literature, the works of Sade will likely have a similar moralizing effect. Equally with Lolita. The specific  (dream) content, in these cases, are what drive the moralizing effect.

It is the safe play space of the work of literature (or of the amusement park, for physical dangers, etc.) that allows one to morally develop. While in the real world, actually doing immoral things makes doing those immoral things easier to do over time, when we experience such things in the dream/play space of literature, we see the opposite effect. Literature makes us more moral, because of the content. Violent video games make us less violent in real life. Amusement parks make us more brave in the face of physical dangers because we faces simulated danger in the form of roller coasters, etc.

Does this mean there are no dangers to literature? Was Cervantes being silly by having Don Quixote go mad from reading so many romances? If so, what are we to make of the fact that there were a string of suicides in the wake of the publication of Goethe's The Sorrows of Young Werther? The young men who killed themselves after reading Goethe's novel did so in emulation of the book's hero. Did they empathize overly much? Is there a danger in that with great literature?

And yet, who today commits suicide after reading Werther today? Were we perhaps seeing a rash of suicides that would have taken place anyway? Would Lennon's assassin and Reagan's attempted assassin have gone through life, perfectly normal, had it not been for the publication of Catcher in the Rye? Or are we seeing cases where the readers could not themselves differentiate between dream and reality, between fiction and the real world? How is that the fault of the work itself, that there are such readers out there? And does this not in fact prove my thesis?

These are all questions which need to be more fully investigated. But I think it is clear that literature has a major effect on our moral development, primarily through the development of empathy. This in turn is going to affect our various moral orders, including politics, philanthropy, religion, philosophy, and the social sciences. That being the case, it is vital we come to understand how we interact with literature, and what the consequences of those interactions are for ourselves as individuals, for those we know, and for the spontaneous orders in which we interact.

Progressives Are Nothing But Jerks and Ought to be Taken Out and Shot; Or, Group Dynamics: Problems and Solutions

One of the more helpful contributions of postmodernism and postcolonialism is the development of the concept of the Other. What were once thought of as separate issues -- sexism, racism, homophobia, etc. -- can be seen in this light as deeply structurally related. This is important in no small part because it can help us overcome the utter nonsense of the claim that sexism, racism, etc. are entirely socially constructed and help us realize that what we are in fact dealing with are particular expressions of an evolved psychological tendency.

Humans naturally engage in "othering." We see it in children. Put a group of children together, and they will form smaller groups, and those smaller groups will in no small part create an identity based on the fact that they are not the other group(s) that formed. The formation of the group can be as arbitrary as mere proximity; yet, when the groups are formed, they are quite clear about who is "good" and who is "not as good as us." From an outside perspective, each group may be essentially the same, with the same mixture of race and sex and ages, but if you were to ask each group about themselves and the other group(s), you would find each providing many good attributes about their own group, and finding all kinds of flaws with the other group(s). Anyone who has seen children in a classroom and/or on a playground knows this to be true.

In the past, group membership was something you were born into. Your tribe was US, and other tribes were THEM. And the name of your tribe typically was the same word you had for Human Being; others in other tribes were not fellow human beings. Out of this we see the old patterns of racism, ethnic divisions, religious divisions, etc. As divisive as religion often is, it has nevertheless acted as a way to overcome racial and ethnic divisions. Race does not matter so long as you are a fellow Christian, Muslim, etc. A shared Other can make for a larger group of Us.

However, the world is seeing greater and greater heterogeneity. Especially in places like the United States. We send our children to school with children of other races, ethnicities, religions, etc. We see them playing together and getting along, and come to the conclusion that racism is socially constructed -- after all, look at our children playing, showing no racial animosity at all. But this actually exposes our own racism, in thinking that what children are looking for are deep, inherent racial differences that are, in fact, not really there. However, if we understand what we are really looking at, we can see that our children are no better than any other human being that ever lived -- they just Other different groups.

And sometimes they do the same old Us vs Them groups. Your children will fight like cats and dogs -- until and unless someone else comes along, in which case there will be a united family front against the other. Outsiders cannot attack the family.

It is more obvious when we look at how our children divide themselves up now. It is less and less along racial/ethnic lines and more and more along lines of interest, etc. Cliques are the new "racism." The nerds are certain they are superior to the jocks, who are equally certain they are superior to the nerds. You have nerds, geeks, stoners, punks, gangstas, jocks, etc. It is Our School vs the Other School(s). My college vs. other colleges. My sports team vs. other sports teams. Science vs. the Humanities. Proletariat vs. Bourgeois. Right vs. Left. As we get older, we simply change group membership -- we don't abandon group membership itself.

Political divisions are a good example of this. The Right is convinced the Left are immoral, arrogant dictator-wannabes. The Left is equally convinced the Right are immoral, arrogant dictator-wannabes.  Libertarians agree with both of them, and both of them agree that the libertarians are out of touch with reality (and arrogant and immoral). The divisions become deeper and deeper the more there is at stake -- and the more power the government has, the more there is at stake, meaning divisions are only going to become deeper and deeper.

The divisions humans create may be arbitrary in many ways, but the fact that we want to divide ourselves into Us and Them is an evolved drive. That drive is not socially constructed, though the qualities of the divisions may be. We are naturally xenophobic. However, we are naturally xenophilic as well (making us paradoxical in nature -- meaning we have to engage in complex behaviors to negotiate both drives). We are naturally competitive, but naturally cooperative as well. And the latter drives the former. We cooperate to compete. We get together in groups to cooperate, but that means we identify other groups with which we are in competition. So long as the stakes are relatively low (power and wealth relatively decentralized and spread out, as one finds in market economies), the groups will not engage in violent competition. Violent competition is costly, and the benefits have to outweigh the costs. This means that if the stakes get to be high enough, violence becomes worth engaging in. This is the great danger in governments having too much power over peoples' lives, whether in the economy or in other aspects of civil society. The more power a government has, the more there is at stake. The more there is at stake, the more likely it is that the groups in a given civil society will treat each other with increasing hostility.

We are never going to get rid of the human tendency to want to live together in cooperative groups. Nor would we want to do so. It is what allows us to live in cities and work together in firms. But that same tendency has a dark side. Depending on what institutions are in place, that dark side can be greatly minimized, or it can be greatly emphasized. If we centralize wealth and power, we can expect greater hostility among groups. If we decentralize wealth and power, we can expect decreased hostility among groups. But we will never get rid of the natural human tendency to get into groups and to think our own group superior to others. We can only create the conditions to mitigate those effects.