Another success for FoldIt

David Baker‘s group has had another success for FoldIt, their computer game for folding proteins.  As reported in Nature News, Victory for crowdsourced biomolecule design, FoldIt players managed to improve the computer-designed enzyme that catalyzes Diels-Alder reactions.  I’ve not read the paper itself (Increased Diels-Alderase activity through backbone remodeling guided by FoldIt players), which is hidden behind a paywall (though UC has a library subscription, so I do have access).

The initial impressive feat from Baker’s group was that they designed an enzyme de novo using Rosetta design (this was reported in 2010).  The FoldIt addition was an 18-fold increase in activity, which came from targeted redesign (redesigning a loop to increase contact between the protein and one of the reactants, stabilizing the new loop, and so forth).  The FoldIt players were not not choosing the goals of the redesign (that was done by postdocs in Baker’s group), but they were exploring the protein space in ways that conventional optimization programs do not (such as adding 13 amino acids).

This is not the first success for FoldIt.  They had a Nature paper in 2010, which reported on the success of FoldIt players at predicting protein structure on a target that had eluded automatic methods for a few years.

So far as I know, FoldIt is the only computer game so far to have made any real advances in molecular engineering. (The main other contender, EteRNA, though fun to play, does not capture enough in its scoring function for EteRNA play to do anything very useful.)

Disclaimer: my former PhD student, Firas Khatib, was an author on both the FoldIt papers mentioned here, though he was not part of the original enzyme design team.

Arsenic-based life was bogus

For those who have been following the news about the surprising claim by Felisa Wolfe-Simon that a bacterium isolated from Mono Lake incorporated arsenate into its DNA backbone in place of phosphate, there seems to be some pretty strong refutation of the claims now.  (I blogged about it twice before: when the story first came out and later when the experimental refutations were beginning to come out.)

Rosie Redfield have openly posted data using better lab procedures that show no arsenic in the DNA. The latest post in the series addresses some incorrect assertions about Dr. Redfield’s protocols that appeared in the Nature News article Study challenges existence of arsenic-based life.

With this new data, the burden is clearly on Dr. Wolfe-Simon to either retract her paper or provide some more convincing evidence for her astonishing claim.  I am doubtful that Science will put any pressure on her to retract, since they have a long history of presenting sensational, but wrong, science papers.

Learning to use I2C

For the Santa Cruz Robotics Club, I’ve bought three sensors for their underwater ROV: a magnetometer, an accelerometer, and a pressure sensor.

Originally, we were going to an ADXL335 accelerometer (with a breakout board by Adafruit Industries) and an MPXHZ6250A pressure sensor (no magnetometer), for which I designed a small PC board, but once the specs for this year’s mission came out, we saw that they wanted us to determine compass headings for a “sunken ship”, so it seemed a natural thing to add a magnetometer to the hardware.  After looking at what was available, I chose the MAG3110 breakout board from Sparkfun, because it provided a triple-axis magnetometer for only $15.

The MAG3110 is an I²C interface, which means we need only 2 wires to hook it up (and the wires can be shared with other I²C devices).  If we are going to all the trouble of figuring out an I²C interface, I figured we might as well use it for the accelerometer as well, so I got a MMA8452Q breakout board from Sparkfun also.

I decided to do a simple test program for the I²C parts before handing them over to the robotics club, so that they could be sure they had working parts.  It was a good thing I did, because I spent more than an entire day trying to get the parts to work.  I finally gave up on the “Wire” library from the Arduino website, and tried using the i2c.h file from Sparkfun (example code linked to from the accelerometer web page).  I got that working and rewrote the library as a proper .h and .cpp file, so that it could be installed as a normal Arduino library, adding some of the utility calls that had been buried in the MMA8452 demo code.

The MMA8452Q code was working fine, so I tried using the same i2c library for the MAG3110 magnetometer.

I had gotten MAG3110 working with the Wire library, but running at 5v (I’d not noticed that it was a 3.3v part—rather, I thought I’d checked that it was a 5v part, but I was wrong).  I’d left it powered at 5v all night, and I think I burned it out, as it was quite warm in the morning.  Today, I can read and write the registers of the MAG3110, but the xyz values are not coming out reasonable at all—I frequently get the same values (like 0xF9F9)and 0x1DF9), independent of the orientation. If I read all the registers, a lot of them come out as 0xF9 or 0x1D.  Even the WHO_AM_I register (which should be 0xC4) often comes out 0x1D.  I seem to get intermittent correct values for registers, but mostly bogus values.

I’ll feel stupid if I order another part and it turns out to be a software bug, but I’m pretty sure the chip is fried.  But I guess it is time to do another Sparkfun order. (I owe them some business, after calling them for the replacement photointerrupter.)

Incidentally, I tried finding a usable pressure sensor with an I²C interface, but it doesn’t look like anyone is making them except for barometric pressure ranges for dry gases.  I suppose Freescale will eventually come out with a full range of I²C pressure sensors, but my guess is that will be a long time coming, as the automotive and industrial applications have a pretty long product design cycle (unlike consumer electronics, which is driving the barometric pressure sensors).

Soldering problems

In Newton’s measurement of g, I said “In preparation for this, I had bought a “photo interrupter” from Sparkfun and a breakout board to mount it. (Actually, I ordered 2, which was a good thing, since one of them did not work—Sparkfun is sending me a replacement).”

I think I owe Sparkfun a couple of bucks for that replacement, because I now no longer believe that the part was faulty.

The replacement part arrived yesterday, so this morning I unsoldered the part that I believed was faulty and put in the new one.  Getting the holes clear enough to insert the new part was a bit difficult with just a soldering iron and a solder sucker, but I eventually managed to do it.  Since I already had the good photogate set up for the physics lab, I did not get a chance to test the spare until after lab was over.  It didn’t work either!

Now, I’m willing to believe in one random part failing, but two in a row seemed unlikely.  That lead me to suspect problems with either the soldering or with the breakout board.I had already checked thoroughly for shorts (I always do that before powering up a board), and I knew there were none.

I had noticed when taking pictures of the photogate that the IR LED is clearly visible on the camera’s LCD display (strangely, it comes out looking blue, not red), so I looked at the IR diode through the camera—not lit up!  I double checked with the good part and it lit up very visibly.

I then checked the bad board for open circuits.  I quickly found that the resistor, which should be connected on one side to the ground plane was not connected to the ground pin of the header.  I re-examined all the solder joints, and one of the ones on the resistor looked a little bit less than perfect, so I reflowed the solder joints on the resistor.  Still nothing.

In desperation, I tried reflowing the solder joints on the header, although they all looked good.  Success!  It seems that the solder to the ground pad, though looking like a perfect connection, was not connecting. Now the second photogate is working just as well as the first, and I’m feeling very sheepish about having trusted visual inspection of a solder joint—I should know better than to do that.  I certainly should have done a better job of debugging before complaining to SparkFun, who were very nice about replacing the part, no questions asked.

So what can I do?  I feel I owe Sparkfun for the $1.95 part they sent me, but I’m not sure that the effort to get them the money wouldn’t cost them so much in labor costs for handling something unusual that they would lose money on my attempt to pay them.  About all I can do is encourage others to do business with them, since they seem to have real superb customer service.

If anyone does get Sparkfun’s photogate and breakout board, look at the easy Lego mounting I have in More on pendulums, which was easy to set up and worked very well. And check your solder joints carefully!

What I’m teaching next year

The Curriculum Leave Plan for our department was just approve by the Dean, so now I know what I’m teaching next year:

Fall

• How to be a grad student.  That’s not its official name, but that’s what its purpose is.  I created this course and have taught it (except for Fall 2011) ever since.  I’ll find out if anything new was added this year, but otherwise this course is pretty straightforward for me to teach.
• Bioinformatics: Models and Algorithms.  I’ve been teaching this forever also.  I definitely plan to talk to the person who taught it this year, as we may be alternating years from here on, and I’d like to incorporate any novel stuff he did.

Winter

no courses, but I’ll have to do some course design and prep work for Spring

Spring

• Introduction to Programming for Biologists and Biochemists. I’ve never taught this course—for that matter I’ve never taught any large introduction-to-programming course, so I’m definitely going to have to do some prep work.  I need to find out what has been taught in this class in the past, what pedagogical tricks are needed to get math-phobic biologists to program, what texts (paper or on-line) are available and suitable, and so forth.  I suspect a big chunk of my winter quarter will be prepping for my first lower-division course in over a decade.
• Senior Thesis Presentation. I assume that this course is an attempt to get the senior thesis students to write their theses and prepare poster and oral presentations.  It strikes me that the last quarter of senior year is far too late for this.  They needed to start writing their senior theses when they started doing the projects updating drafts as they go, but I doubt that even one in ten will come in with an outline, much less a draft. Half of them probably will not be able to reconstruct what they have done from their inadequate notes in their lab notebooks, since their research advisers never made them write anything up in any detail and never looked at their lab notebooks or taught them what to record. (Not all the research advisers are so unhelpful with their undergrads, but enough are to make this course be too little, too late.)
  I’ve done something like this before, but a quarter earlier in the year, when students were still working on their thesis research.  The work load for providing student feedback is incredibly high (practically a full-time job for just this one course), and I expect it to be worse this coming year.

There are no surprises for me in the official CLP—these are the courses that I had agreed to.  It is a higher than usual load, because the budget cuts meant we could not afford to hire instructors for some of the courses we usually use them for, and I volunteered to take on the intro programming course, so that we could continue to hire a lecturer for the popular Human Genome course.  It isn’t quite as high as the load I had last year, so I should survive it, but Spring will be rough.