Thesis Defense: How Helical Junctions Determine the Folding Stability and Allowed Conformations of Structured RNAs

Title:

“How Helical Junctions Determine the Folding Stability and Allowed Conformations of Structured RNAs”

Abstract:

Structured RNAs are inherently dynamic, exploring a diverse set of conformations within the cell. Understanding the physical origins of their folding stability, motion, and interactions with other biological actors will require characterizing the conformational landscapes they explore. The simplest motifs within structured RNAs are two helices joined by non-helical junctions. To dissect the thermodynamic properties of these fundamental helix-junction-helix (HJH) motifs, we computationally probe how junction topology, electrostatics, and tertiary contact location contribute to the folding stability of a simple tethered duplex model system. We then extend this work to construct a map of the allowed conformations of the Transactivation Response Element (TAR), a HJH motif extracted from the genome of the Human Immunodeficiency Virus. This conformational map, analogous to the Ramachandran plots for proteins, can aid in the interpretation of experiments by showing how experimental data fit into the context of the allowed conformational space. Our results indicate that the simple constraints of a single- or double-stranded junction, independent of sequence, profoundly influence the preferred location and orientation of the adjoining helices, helping to determine the folding stability and specificity of the motif. These sequence-independent effects suggest that properties as simple as a junction's topology can broadly determine the conformational landscape, stabilize desired structures, and assist in discriminating against misfolded structures, providing an additional strategy for transcending the limitations imposed by the low information content of RNA primary sequence.

Date: Thursday, October 29th, 2009 - 2pm
Location: Clark Center, S360

It's a chemical party!

Simple perl script for downloading entire books from myilibrary.com

Wow. People really want to download books from myilibrary.com. They restrict downloading, even to students who have legitimate access to their books through their universities. I was somewhat annoyed by this, so I wrote up a quick 5 minute script that would download entire books from Myilibrary.com and posted it out of pure frustration with their stupid policy. Since then, I've gotten a lot of people coming to that post through google.

I've had a few requests for this script so I'm posting it up here. Remember, this script is an old script (I haven't used it for awhile) so I don't know if it will still work. Second, this script will only allow to automate the download process to books you already have legitimate access to (usually through your school or university). Third, you can only download about a hundred pages a day, so you'll have to split your downloading of long books over several days. Fourth, I have no interest in maintaining this script or answering emails about how it works-- I needed it to download two books, and once that was done, I haven't touched the script in several months. If you need more details, check the notes I made that will give a reasonably tech-savvy person everything he needs to know.

[UPDATE: I've been asked to remover this content by a DMCA Complaint initiated by Ingram DV LLC. However, that's not to say any reasonably tech-savvy person couldn't figure it out.]

Nerdy Image: HIV Transactivation Response Element

My research of late has been going well -- recently I've been exploring the behavior of the Transactivation Response (TAR) Element found in Human Immunodeficiency Virus (HIV) using a variety of computational tools.

The TAR element is an essential part of the HIV lifecycle and is found within the RNA genome of this virus. In an infected cell, the interaction between the TAR element and other proteins is responsible for a dramatic increase in the production of viral proteins. The TAR element has also been shown to inhibit programmed cell-death by infected cells, allowing the process of viral replication to continue unabated.

The snapshot I've attached is taken from a simulation I'm running and highlights certain regions of the TAR element, solvated in an environment of water. The isolated spheres are sodium ions.

Bogosort - Wikipedia, the free encyclopedia

Learning and Scientific Reasoning: Chinese Students Compared Against American Ones

Ever since I was a kid, my parents have told me how rotten and lazy
American students were and how Chinese students, with their diligence
and work ethic, would inherit the world due to their superior
education. If that weren't enough, there's the constant drumbeat of
our own media decrying the crisis in our schools, the poor conditions,
and the lack of accountability.
 
Now of course I'm not suggesting that our students can get away with
being lazy or that our schools don't face immense challenges preparing
the next generation of students. But I also think our schools have
many strengths and that such strengths are often under-appreciated.
For instance, consider this study just published in Science magazine
comparing Chinese and American students.
 
In China, students take a standardized national curriculum with 5
years of physics courses. America, on the other hand, contains a
greater diversity of approaches, and thus students have not had much
formal training in physics. So, in a test of physics knowledge and
scientific reasoning administered to freshman college students, who
would do better: the Chinese or the Americans?
 
Unsurprisingly, the Chinese outperform American students on tests of
physics knowledge --- things like mechanics, electricity and
magnetism. They killed us on all of those problems with balls, ramps,
pendulums, circuits, charges, etc. But the surprising thing was that
American students matched the Chinese on scientific knowledge! That's
right --- in the study, there were essentially no differences between
Chinese and American freshman students.
 
So what does this tell you? On one had, it should be sobering that our
students knew so little about physics, an essential topic that every
educated person should know something about (disclaimer: I'm a physics
student). On the other hand, we have much to be proud of -- our kids
have the right stuff when it comes to reasoning. Where did they get
this from? Probably from the way they were taught, which in America
means a diet of inquiry-based courses where thinking is emphasized
over rote memorization.
 
One could even see this result as an indictment against the Chinese
educational system; despite much more training, Chinese students seem
to have picked up only the facts, an conclusion that was also reached
in the study:

The results from this study are consistent with existing research, which suggests that current education and assessment in the STEM disciplines often emphasize factual recall over deep understanding of science reasoning

 
Of course, we shouldn't rest on our laurels -- American education is
still broken in many ways. Our schools are still failing them, but
perhaps not in the way you might think. But the results of this study
show that in our drive to improve our educational systems, we musn't
throw out the baby with the bath water and wholeheartedly embrace a
testing-only based curriculum. That is to say, we must not discard the
very things that make our educational system great.
 
Caption: Content knowledge and reasoning skills diverge. Comparisons
of U.S. and Chinese freshmen college students show differences on
tests of physics content knowledge but not on tests of scientific
reasoning.
 
Taken from "Learning and Scientific Reasoning", Science 30 January
2009: Vol. 323. no. 5914, pp. 586 - 587

Science and Democracy

If we are not practicing good science, we probably aren't
practicing good democracy. And vice versa.

 
Probably the best quote from Dennis Overbye's essay "Elevating
Science, Elevating Democracy" that appeared today in the New York
Times. One of the greatest misconceptions about science is that it is
a body of facts to be memorized. The persistence of this myth has
everything to do with science's presentation in our educational
system, from the primary level all the way into our universities. Of
course, nothing could be further from the truth. It is true that
science deals with facts; however, the true kernel of science comes
with the human thought that links those facts into ideas and a
coherent framework. The true kernel is the debate and argument and the
constant tension that is applied with each successive generation to
those facts.
 
http://www.nytimes.com/2009/01/27/science/27essa.html

Peace. Love. Biophysics.

Part of the schwag I received from the single molecule biophysics 2009 conference at the aspen center for physics.
 
Unfortunately I missed out on the sweetest gift of all: a "Mendel is my chrome-boy" stein glass. Maybe next time. Nevertheless, the mousepad does kick ass.

Posterous as Journal Club

Since I'm now sort of a member of the Posterous family (well, pretty
much on the fringes, maybe somewhere above a half-third-cousin by
marriage, but below a second-cousin, once-removed) I've been thinking
about interesting derivative applications for Posterous (mainly as a
way to avoid work).
 
I've been stuck in paper-writing hell for awhile now; today was no
different. Part of the paper-writing process (and more broadly, just
day-to-day academia) is reading papers and references pertinent to the
topic that you're writing about. So today, I found myself reading a
paper on single-molecule GAAA tetrtaloops, wishing for additional
context and feedback.
 
You see, reading academic papers is one of the loneliest and most
difficult parts of an academic's life. It's not enough to simply read
papers, you have to read them critically and skeptically --- what are
the holes in their arguments? Are the data correct? What are they
trying to hide or downplay? What's the context of this study?
 
Academics typically solve this problem by holding informal journal
clubs, meetings where people meet and discuss relevant papers, dissect
them, tease them apart, and otherwise try and read the literature
critically. Everybody benefits by having tons of eyeballs on the
paper. However, I've always found journal clubs to be horribly
inefficient -- gathering people together is difficult because of
conflicting schedules and it's hard to do this for all of the papers
that come out. Really, for any given paper, all you want as a reader
are quick comments on their techniques, or on points that you find
fishy.
 
So, I was thinking that Posterous could become a nice platform for
that -- I could set up a posterous site, then email a PDF of the paper
I'm reading. Poseterous handles all of the posting and people ---
colleagues, collaborators, or other interested parties --- could
simply comment below the paper. Sort of like minutes for an
online-journal club! That way, we can get quick comments on papers out
without having to resort to the cumbersome face-to-face journal club
meetings.
 
Of course, this idea isn't new. This is basically the main model
behind PLoS One ( http://www.plosone.org/home.action ), the
blog-arXiv-publisher-mashup. But the problem is, PLoS One is only good
for papers published through the PLoS One infrastructure.
 
The only problem is that these PDFs are copyrighted and not can't be
published online (legally)..

A repulsive field: advances in the electrostatics of the ion atmosphere

Seems like all I do these days is publish review papers. I'm not
complaining -- a paper's a paper is a paper.