Chemists, controls, and computing.

I have no experience with drug discovery, so I suggest one reads the excellent commentary offered over at The Curious Wavefunction and In the Pipeline inspired by a recent article on the role of computer simulation in pharmaceutical research, presuming that they haven’t already done so. What I thought was interesting enough to post about in response is in Wavefunction’s blog post.

They are reluctant to carry out the kind of basic measurements … which would be enormously valuable in benchmarking modeling techniques.

Methods development research can be difficult to support. Even obtaining modest funding can be difficult. It’s one reason why it can usually seem incremental in nature, as it’s easier to scrounge a few small devices or specialty materials to use with existing research infrastructure. This one is near and dear to my heart, as I have two such projects going on at the moment, and a third which is still in the planning stages. Unfortunately, it’s not the kind of stuff one could convince people it needs to be funded and generously at that. That was really more just me griping. But that is par for the course for me here at my blog…..

Unlike chemists, engineers are usually more naturally inclined to learn programming and mathematical modeling. Most engineers I know know at least some programming. Even if they don't extensively write code they can still use Matlab or Mathematica, and this is independent of their specialty (mechanical, civil, electrical etc.). …The lesson to be drawn here is that programming, simulation and better mathematical grounding need to be more widely integrated in the traditional education of chemists of all stripes, especially those inclined toward the life sciences.

I of course agree, but am inclined to mention a few things. This may be an artifact from my recollection/experience and is no longer the case, but I’ve seen a tendency for computational methods & applications courses intended for chemists to be heavy on the typical computational chemistry aspects (basic electronic structure calculations, a dash of MD, some molecular mechanics) along with a fair bit of introductory programming. Not that there’s anything wrong with that….but wait, actually, it is problematic.

I would think a more useful course might still contain some introductory programming and some of the typical computational chemistry, but I’d like to think that one could also take the time to introduce the students to chemo/bioinformatics as well as a module on proper data fitting. Of course, it might be claimed that it’s better suited for an upper-division chemistry laboratory, which would be fine. The important thing is to get people weaned from MS Excel and to actually start fitting data, not algebraically torturing your data until it’s in a format that can be linearly plotted and then fit with Excel.

Also, given that I have this notion of this course being something that all students will probably find useful in the future, the programming and software elements should be those that will easily lend themselves to a broad range of applications and uses in the future. I would imagine that introducing students to something like Origin or Igor Pro would be useful, as well as (re)introducing them to Mathematica, Matlab, Maple, or other comparable software. While the power of Fortran is well established for the numerical-heavy applications in computational sciences, I feel it would be better to have students introduced to something like Python. You can leave the Fortran for those who want to do the computationally intensive theoretical chemistry, while I’m sure the majority can use Python as a useful tool in their work.

This above is clearly influenced by personal biases (I'm a bio/physical chemist who is in the process of adding "systems biologist" if he keeps it up for much longer), but I think that sort of mix in a "computers & chemistry" course would serve a good cross-section of the chemical community. Any and all commentary, feedback, suggestions, and brutal eviscerations of my points are welcomed. Read more!

Cackling in Glee.

I actually can't muster up any of my lazy man's wit for this year's chemistry Prize - is it physics? Physical chemistry? Materials science? Just sublimely wonderful and scoffs at the narrow cognitive categories that spring up on occasion. It also emphasizes that as chemists, we have fellow travelers in numerous allied pursuits - remember, if we want to continue blaring the "we are the central science" mantra, we have to recognize chemistry of all sorts whatever its ostensible classification.

The comments at ChemBark brought up two questions in my mind -

(1) - what do we consider chemistry?

and

(2) - why did it seemingly not catch anyone's attention as a candidate for the Chemistry Prize?

I've mentioned - in the vein of Roald Hoffmann - that chemistry stands on the pillars of structure, reactivity, and synthesis. Anything that causes us to reevaluate our understanding of even one of those pillars is noteworthy, as quasicrystals surely did in terms of understanding structure. That they can also occur naturally would indicate that our understanding of geochemistry can stand some fleshing out.

Now, if you had asked me about quasicrystals yesterday, I'd have thought that they'd be a Physics Prize one of these years, given that most of what I had heard about them was through physics seminars I'd attended over the years. But it used to be that the gap between physics and chemistry was far smaller - Rutherford (he of the physics vs. stamp collecting joke) picked up his Nobel in Chemistry way back when, and van der Waals was a Physics laureate. This year's Prize is a nice throwback in that regard. I think there might also be something to the comments on ChemBark that solid state chemistry is something of an underexposed topic in undergraduate curricula here in the US, and many of us just don't have that proper background in the field (which is certainly my case - most of what I know is because I stumbled into having learn something about the field in grad school). There might also be an echo chamber effect going on in the chemistry blogosphere. ;)

Now to start preparing for next year's betting pool! Read more!

Nobel Notes

Thumbs up to the Nobel Foundation for their decision regarding Ralph Steinman's laureate status. I always felt that the rule was to make sure nominations of those who have passed on were not submitted in the first place. Now, whether or not one agrees with this is a separate issue.

Given that my professional interests are not very immunological or astrophysical, I don't have any particularly incisive commentary about the Physiology/Medicine or Physics Prizes.

A followup to a comment elsewhere - Tom Wainwright passed away in 2007, so unfortunately he would be ineligible for a Nobel. Given that Aneesur Rahman and George Vineyard have also passed on, Alder is really the only "founding father" of MD who would be a possibility.

On the off chance it is a magnetic resonance Chemistry Prize this year, I will not be sarcastic and post "but it's just applied physics! Why are applied physicists winning Nobel Prizes?" I'll actually just write a short blurb on what was so cool about the new laureates' research. (All other fields of physical chemistry being recognized are fair game for such commentary, though.) Read more!

Surely you jest!

So, I strongly recommend everyone checks out this paper -

Accessing protein conformational ensembles using room-temperature X-ray crystallography

- which was just published in PNAS this week. The paper cites a 2004 paper by Bertil Halle (which I mentioned a while back) on the potential consequences of flash freezing and cryocrystallography.

Enjoy! Read more!

No, I am not going to talk about the recent paper on the success of Foldit. Mostly since if you can even get a crystal structure for something, it's probably not agonizingly painful enough for me to work on - as I've said before, give me your disordered, your poorly soluble, your aggregated masses yearning to be analyzed.

Anyway, I wanted to mention this interesting-looking paper:

Binding Leverage as a Molecular Basis for Allosteric Regulation. I haven't had a chance to really dig into the paper, but the idea itself is simple enough - ligand binding can couple to various collective motions in proteins to varying extents, due to which we observe allosteric modulation of enzyme function. There are obvious oversights (one example that they mention in the paper - the lack of attention paid to proteins that aren't enzymes such as signaling proteins of various types), and I'd want to pore through which structures they used in the PDB (e.g., how did they deal with the family of structures that are generated by NMR if applicable). Then again, I usually consider thought-provoking ideas worth the publication, even if a judiciously skeptical outlook may make them seem a little less lustrous. Read more!

As it’s that time of the year again to start speculating about potential Nobel laureates for 2011, I’ve already chimed in at The Curious Wavefunction and left a short note over at ChemBark.

While I’d be pleased to see another magnetic resonance prize (or five), there is a huge name which I’ve neglected, mostly since I was afraid that his time to be recognized had passed, but as he was the Welch Award recipient this year – John Waugh from MIT. Of course, if it were up to me, I bet I could come up with at least half a dozen trios of deserving recipients for magnetic resonance. But anyway…..

I’ve wondered about this earlier and I might as well bring it up again – what about the Kavli Prizes? Currently, they’re awarded for astrophysics, nanoscience, and neuroscience – will see ever see a dual Kavli and Nobel laureate? Or will being recognized with one put you out of the running for the other? Having said that, I know people were predicting someone getting a Nobel for semiconductor nanocrystals, so perhaps if Lou Brus is recognized by the Nobel committee, we’ll see one this year.

Quantitative biochemistry is not giving me quite as much of a headache. Although I'm hardly done with it just yet. I do envision there being an extremely dense biochemistry publication in my future. Speaking of which, back to working up data.... Read more!

A few quick thoughts.

I am still trying to unenviably navigate an n-dimensional parameter space, attempting to optimize the biochemistry for the present bane of my existence in order to get to some proper structural & biophysical studies. It is further complicated that whenever I do seem to devise a plan, something odd crops up in my data in amidst the general experimental madness (remember, if you work with n components, you need to vary one and keep n-1 constant : easier said than done!).

In any case, I stumbled across this interesting paper. Given my innate worrying about structural data obtained under cryogenic conditions, this was right up my alley – utilizing mesoporous materials to confine proteins and their hydration waters, and then using your interrogation method of choice across a range of temperatures without having to worry about the effects of bulk water. I can envision that this would be an excellent way to more explicitly bridge the gap between cryocrystallography and dynamic/functional studies done under more physiologically relevant conditions.

There was a very long back-and-forth over at The Curious Wavefunction this past week. I basically have the opinion that expecting physics to “explain” chemistry and biology is perhaps a bit overly demanding. I mean, it’s not as if all physicists are just waiting to wrap up high-energy/elementary particle physics and then retire, after all! There are still a number of unresolved questions in physics, and as a number of them involve many-body systems, it would only seem reasonable that those are the ones that would likely be of the most immediate application to chemistry and biology.

Now to finish preparing for this inclement weather…..
Read more!