Nobel Notes (Pt. II)

Upon request.....

Molecular Dynamics

So if we skip over the entire Monte Carlo simulation work, the first proper MD work was Berni Alder and Tom Wainwright in the late 1950s on hard-sphere systems.  Wainwright, as I noted last year, passed away a few years ago.  George Vineyard (Brookhaven National Lab) used MD to study radiation damage right around 1959/1960, and Aneesur Rahman did the first MD simulations of an actual liquid (for the pedants - yes, I know it was argon) in the mid 1960s.  Unfortunately, neither Vineyard and Rahman are still with us.

Here it gets more complicated, as the move to more "chemical" systems involved a number of people (David Chandler and Bruce Berne among others).  And then there's developments like ab initio MD (Car & Parrinello in the mid-1980s) which have been more on the fundamental side, in terms of bridging MD to DFT in this case, and has found plenty of application (Car & Parrinello were jointly awarded the APS's Rahman Prize for Computational Physics a while back).  


Magnetic Resonance/NMR

So, I really do think solid state NMR has a prize with its name written on it.  It's obviously been a while in the making, but it is finding great use in multiple areas of application (chemistry, structural biology, polymers & materials, and various subfields and intersections branching off from these).  My general feeling is that it would be tricky to award a Nobel for solids NMR without including Alex Pines (Berkeley), as he's had his hand in the development of cross polarization (which basically everyone uses, whether you're doing static solids NMR or magic angle spinning solids NMR), as well as contributing to multiple-quantum NMR spectroscopy, quadrupolar NMR methods, and various other proofs of principle and applications (investigations of the Berry phase by NMR to his more recent efforts in combining optical pumping and hyperpolarization for imaging purposes).  There are other names here, but it gets tricky.  I suppose Pines' former graduate advisor, John Waugh, could be here as well.  And there's always the risk I'm forgetting someone, since I'm sure there's some paper from 1975 that I haven't read (or whenever). 

I think I've brought up Harden McConnell before, not only for his contributions to NMR but also for his work in EPR and its applications to understanding biomembranes, including early work in spin labels.  Of course, I'm sure people will gripe about the fact that his more recent work was biochemistry and immunology-oriented.  Heh.

I wouldn't object to Ad Bax being included, but I can see where it might be hard to convey the Nobel-quality novelty after Wuthrich's prize 10 years ago or so now.   I know he's tremendously well-cited - heck, I've cited him! - and always places very highly on those h-index rankings, but I could see this being an uphill battle to some extent.

So that's that, at least for now, I'd say.




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Nobel Notes

I am not even going to try and offer up any predictions or suggestions given last year's surprise.  I will, however, make a few comments, some of which I've mentioned in the past.


Molecular Dynamics

Martin Karplus is usually mentioned here.  Chembark has this folded into a more general computational chemistry prize with other scientists who have contributed greatly in other areas of comp. chem., as has the listing over at the Curious Wavefunction.  Not to take anything away from Prof. Karplus and his extraordinary career, but as was brought up last year, this position betrays a lack of appreciation for the development of MD.  I'm not sure how one could reward Karplus without snubbing the early accomplishments under the rug that showed the power of computational methods to ask questions and provide answers to physical problems.  Of course, it's also entirely possible that an MD prize would be one in Physics, which would be entirely acceptable as well.

GPCRs

While some have noted that a Prize for the recent structural accomplishments might seem premature, I can envision a slightly different scenario.  Kobilka's former mentor, Robert Lefkowitz, did receive the National Medal of Science a few years ago for his pioneering work in GPCRs, and has earned various other accolades over the years.  It's possible that there might be some sort of Prize that involves more on the biochemical side of things, but with an eye (and inclusion of) the structural work.

Magnetic Resonance

Not even going to try since I'll just keep babbling on for a while.

The Kavli Question

Will we ever see a dual Nobel/Kavli Prize laureate?  Or is the work that the Kavli Prizes recognize too interdisciplinary to make it through the Nobel process?  (Cue the whining of chemists who want to eliminate biochemistry from eligibility for the Nobel Prize.  Heh.)

P.S. - Really kind of hoping a physician wins the Nobel for chemistry, a chemist wins the Nobel for physics, and a physicist wins the Nobel for physiology/medicine.  It would be a tremendously hilarious week.









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Trust but verify.

The question of how much to trust computational methods is brought up here at Chemiotics II. My answer is that it depends on what one is looking for in the first place.

If one is looking for some sort of completely accurate and precise way to have all biological phenomenona fall out of "first principles," well, I wouldn't hold my breath. Of course, I don't think anyone is really waiting for that. At least I hope not. I believe my feelings on these sorts of issues are best described by personal experiences I've had with computational methods.

In grad school, I had an interest in this one mid-sized protein (somewhere between 40 to 60 kDa) that was known to bind this particular ligand. There was a crystal structure of the protein with and without ligand, although of course it was hardly the entire story (which is why it was the subject of my research attentions). In any case, collaborators did some MD simulations, and it was consistent with what we had found and was known. In their next bit of work, they mentioned that they found something new regarding the mechanism of ligand binding. This was going on the same time as I was doing some work, and as it turned out, my data did not rule it out. And so new research was inspired for those who took up the project after I left.

Currently, I am embroiled in a sordid and complex tale of transmembrane signaling involving the receptor and varying amounts of soluble cytoplasmic proteins that propagate that signal. There was a fairly recent paper detailing MD studies of the signaling process. Well, part of it, I suppose - huge chunks on either end of the transmembrane receptor were not included, and none of the cytoplasmic proteins that bind and are modified by the receptor were included in the study. Certainly a daring attempt, but it's hard to get too worked up over it when it doesn't resemble anything that I actually work with on a daily basis.

In short....I think properly used, it can be a useful way to bridge what is measured experimentally with the metaphors we use to describe processes. (For example - people love using descriptions involving simple machines, but what is actually measured are thermodynamic or spectroscopic quantities. Of course, "force spectroscopy" looks to change this, but when you yank apart a protein, you are no longer just gently playing around at kT or sub-kT conditions to see what kinds of deformations you get naturally or as a response to some stimulus. Anyway....) Certainly, for small enough systems, I am inclined to give them a proper reading, and in cases where the system might be larger but is somewhat well characterized, the same applies. In giant systems where they toss out a number of critical components or oversimplify to the point of absurdity, I am generally far more skeptical.

Merry Christmas to those who celebrate, Happy Hanukkah to those who celebrate, and a delightful winter holiday season to the rest. Read more!