9 ms·

Computer chemists win Nobel prize

69 points by nsoonhui 13y ago

xerophtye 13y ago
I don't get it. Aren't simulations of chemical reactions based on things you already KNOW about those reactions? How are they being used to find out new things about the reactions?
- josephagoss 13y ago
  I haven't read anything in the link, but I guess that if the simulation system is of sufficient precision and that it is accurate enough for known chemical reactions, such a simulation system should be able to be pushed further and it may end up simulating events and phenomena that have not been observed in the real world before. Bonus points if they observe real world reactions that agree with the model after the simulation has run.
- tlarkworthy 13y ago
  Several generic approaches yield results:- 1. You take a lot of empirical observations of known reactions, build a predictive model, then apply it to contexts you don't have empirical observations of. 2. You program in the low level rules of chemistry (e.g. quantum mechanics), and see how the scenario plays out at a higher level (molecular reactions). I think in their work they are more number 1. A predictive model of proteins without having the simulate the (exceedingly expensive) low level details of QM
- weland 13y ago
  I'm only casually familiar with chemistry, but I used to do research of a similar type (only far worse, of course) related to electromagnetism. You know the main mechanisms at work, but that does not mean you can study all the processes. Sometimes it's just that the sheer size of the mathematical model itself is basically impossible to study without a computer. Oftentimes, though, it's the inadequate formulation of a model that doesn't allow you to simulate it. A good simulation is an immensely useful tool. There are phenomenons which you know and can simulate, but you cannot easily measure their parameters while they are happening (e.g. you risk disrupting the phenomenon because of your measurement installation). I imagine this is even more so for chemists. Real-life example from my own research: we worked on tools that helped engineers who designed really high-frequency ICs (think tens of GHz) study things like cross-talk through the substrate. The mechanism itself is basically well-understood, but save for really, really simple structures that are nothing like those in an IC, you can't solve that by hand. Of course, ours were modest achievements, but the point is that this kind of research can open new gates and shouldn't be considered "second-rate".
- blumkvist 13y ago
  There are programs which allow you to input desirable qualities (smell, color, density, /non/conductor, molecule mass, stereo orientation to name a few, very basic ones) and it will make computations and it will give you possible compounds. Also software in chemistry can be used to simulate reactions and processes, which can take years to analyze with conventional methods(if at all possible), like folding protein chains.
  - varelse 13y ago
    Actually, Vijay Pande's lab has been "folding" proteins in hours to days for years now by massively parallelizing the trajectories: http://en.wikipedia.org/wiki/Markov_chain_Monte_Carlo http://en.wikipedia.org/wiki/Markov_chain_Monte_Carlo Similarly, David Baker's lab has focused on producing the folded conformations of proteins in hours to days using simplified models that are designed for that task: http://boinc.bakerlab.org/rosetta/ http://boinc.bakerlab.org/rosetta/
- deleted 13y ago
  [deleted]
- shiven 13y ago
  You are thinking about reactions as written out in a chemistry textbook. Those representations tell you about the reactants, products and maybe a few other details like catalysts, solvents and temperature. However, none of it explains the mechanism at the quantum or atomic level. Simulating the reaction with specialized software enables you to 'calculate' additional data points, such as, free energy, enthalpy and entropy among others, using 'molecular dynamics' (which 'solves' Classical and Quantum Mechanics equations for a given system and is extremely essential to understand movement of different parts of a molecule and their interaction with surrounding atoms to build a more complete picture of 'how' a reaction proceeds). Today is a great day for computational chemistry. It is good to see the detailed Nobel announcement acknowledge other stalwarts of the field like Peter Kollman (who created AMBER, a package similar to CHARMm by Karplus et al). I have no doubt that Kollman would have received this prize had he been alive today.
  - raverbashing 13y ago
    Exactly Chemistry is applied physics. Chemistry answers that H2 and O2 can be joined to form water under certain conditions, but doesn't answer the "Whys" Physics answers that. And the answer goes around orbitals, energy states, electrons, etc.
    - aristomc 13y ago
      "Chemistry answers that H2 and O2 can be joined to form water under certain conditions, but doesn't answer the whys". Chemistry does answer the whys beyond product yields, why certain elements react is vastly covered throughout organic, inorganic & physical chemistry . It is the basis of these sub-fields, and how this is determined is looking at orbitals, energy states etc...
      - raverbashing 13y ago
        Yes, there's an overlap of knowledge So, Pauli's exclusion principle is Physics or Chemistry? I'd say it's "both".
- sp332 13y ago
  You can simulate the reaction at a quantum-mechanical level at sub-nanosecond timesteps. That gives you a lot of information that you couldn't get from a test tube!
  - varelse 13y ago
    OTOH you can't get sufficient sampling on anything but the smallest systems to make any sort of dynamic prediction about it. Not to mention the approximations that were made during the choice of basis sets for the atomic orbitals and how one decides to handle the configuration interaction. TLDR: Approximations are everywhere, make sure you work that into your conclusions.
  - Xcelerate 13y ago
    I'll clarify that when he says sub-nanosecond timesteps, he means way sub-nanoscale timesteps. Femtosecond timesteps are used at the molecular dynamics level. Even smaller ones are used at the QM level.
dcc1 13y ago
lol @ title
timr 13y ago
Wow. I'm floored that computational structural biology work is getting a Nobel. I spent a lot of time reading their papers in grad school...they're totally foundational for the field, but the field is still really young: Martin Karplus' group is behind CHARMM (http://www.charmm.org http://www.charmm.org), which was the first(?) molecular dynamics package (you can think of it as a precursor to folding@home, though it's still under active development, so that isn't a totally fair statement). Michael Levitt has done a bunch of things, with no one big software package, but he was one of the earliest people trying to do ab initio protein structure prediction. He was also one of the first people to really start categorizing protein structure in a way that allowed for computational modeling -- back in the 70s and early 80s. Arieh Warshel is probably best known for bridging the gap between quantum mechanics and the (relatively quick-and-dirty) molecular mechanics work. He's done a whole bunch of work modeling enzymatic reactions, coming up with better electrostatic models, and other things where quantum mechanics does a good job, but is way too slow to be used on giant molecules like proteins.
- alexholehouse 13y ago
  Don't forget Karplus' colossal contribution to NMR
  - dnautics 13y ago
    yeah, I'd say that is way more important to science. I have never used and never would use CHARMM, Karplus' J-coupling values - indispensable.
  - timr 13y ago
    I had a whole other paragraph about that, but took it out because I figured that most people on HN wouldn't even know what NMR is, let alone NMR structure prediction. These guys have collectively done so much stuff that it's impossible to give a fair accounting of it all in a brief post.
- bbgm 13y ago
  Yes, but I am also not surprised given this is pretty fundamental work, even if it hasn't quite hit the sort of revolutionary goals many of us hoped for. If Peter Kollman had been alive, I suspect he would have shared this Nobel. This Nobel is hits very close to home. Much of my PhD work was done in CHARMM and I come from the Karplus lineage, and at one point in time I had pretty much read every paper Levitt and Warshel had ever written.
fireismyflag 13y ago
I initialy read it as "Chemistry Nobel Prize awarded to chemist's computer"... Makes me wonder if that will ever happen.
jnazario 13y ago
this is pretty awesome. in grad school in the 90s i was exploring a lot of this very early on, very few people around me were there to help and that's ultimately how i got involved using Linux and other FLOSS, then sysadmin, security work and now what i do in computer security research. very glad to see this prize granted for this line of work as it truly was a leap forward for the study of chemistry.
alexholehouse 13y ago
I'm somewhat surprised that Warshel was included instead of Berni Alder, as a more self-consistent group of scientists from a field point of view, and given Alder is largely seen as the father of MD.
- selimthegrim 13y ago
  Well then why not Ceperley too, as they helped straighten out some problems at the core of LDA? I think the Nobel committee wanted to keep the focus on biochem.
  - alexholehouse 13y ago
    Agreed - that's the conclusion I came to too after posting. Still, I'd imagine Harold Scheraga and Andy McCammon are (justifiably) a little sore this morning...
mizanrahman 13y ago
health sector has more scope now to update their process and techniques. I think they should totally rethink their existing methodologies with the power of computation
- varelse 13y ago
  They are. But the previous generation of scientists came of age when Molecular Dynamics was a disappointing tool because of limitations in the Newtonian models and the lack of computational firepower to do sufficient sampling. The latter has been addressed by a combination of Moore's Law and the ongoing migration of molecular dynamics codebases to GPUs, but the former issue remains - a Newtonian approximation to quantum chemistry. What's surprising is how much one can get out of these simple models despite these limitations, something that was echoed back in 1976 by one of Michael Levitt's papers that led to today's Nobel Prize: http://csb.stanford.edu/levitt/Levitt_JMB76_Simplified_representation.pdf http://csb.stanford.edu/levitt/Levitt_JMB76_Simplified_repre...
  - selimthegrim 13y ago
    There are very deep reasons for this - the Born-Oppenheimer approximation, a central simplifying assumption, imposes some constraints on the system that make it easier to model with (semi)classical dynamics, even when you marry it with modern techniques such as DFT. Kieron Burke has a nice take on the matter. http://www.tddft.org/TDDFT2008/talks/KB.pdf http://www.tddft.org/TDDFT2008/talks/KB.pdf see also http://www-fourier.ujf-grenoble.fr/~joye/simon2006.pdf http://www-fourier.ujf-grenoble.fr/~joye/simon2006.pdf, esp. its ref. 93
Xcelerate 13y ago
This is so cool! This is the kind of research I do: molecular dynamics and quantum mechanical simulation. I'm not nearly as good at it as the winners of this prize though haha. I'm glad to see computational research is becoming more popular and accepted. There's a (quickly diminishing) subset of scientists who think computational work is too theoretical, inaccurate, and inapplicable to real-life. This was the case when the field was developed, but it is no longer true. The exponentially increasing computational power is allowing discoveries that simply can not be performed experimentally because laboratory technology just isn't advanced or capable enough. Who needs to actually study reality if you can just simulate what you need -- and the end result is the same? I'm not sure many people know this, but our understanding of the laws of physics is advanced enough nowadays to describe almost perfectly everything we observe in everyday life. (Exceptions include things like quantum gravity which don't really matter [ducks to avoid physicists]). The problem is that if you want to simulate these laws, it requires a lot of computational power. Brute-force approaches are simply ineffective and so simplifications and clever techniques must be developed to reduce the computational effort while giving increasingly accurate results. I think it's the combination of improving computational resources and improving simulation algorithms that are really driving this field.
- dnautics 13y ago
  hey Xcelerate - I'm looking for someone to do some delta-Hf calculations on some "theoretical molecules" for me. By theoretical molecules, I mean, molecules that are very likely able to be made, but needs an assessment of "whether or not it's worth it". Is that something you can do, and would be interested in putting on ArXiV?
  - pa5tabear 13y ago
    What data do you have? Do you know the mechanisms? We calculated heats of formation in our chemical thermodynamics course, but we were always given ample data, and we knew what we were trying to calculate.
    - selimthegrim 13y ago

69 points by nsoonhui 13y ago

I don't get it. Aren't simulations of chemical reactions based on things you already KNOW about those reactions? How are they being used to find out new things about the reactions?

josephagoss 13y ago
I haven't read anything in the link, but I guess that if the simulation system is of sufficient precision and that it is accurate enough for known chemical reactions, such a simulation system should be able to be pushed further and it may end up simulating events and phenomena that have not been observed in the real world before. Bonus points if they observe real world reactions that agree with the model after the simulation has run.
tlarkworthy 13y ago
Several generic approaches yield results:- 1. You take a lot of empirical observations of known reactions, build a predictive model, then apply it to contexts you don't have empirical observations of. 2. You program in the low level rules of chemistry (e.g. quantum mechanics), and see how the scenario plays out at a higher level (molecular reactions). I think in their work they are more number 1. A predictive model of proteins without having the simulate the (exceedingly expensive) low level details of QM
weland 13y ago
I'm only casually familiar with chemistry, but I used to do research of a similar type (only far worse, of course) related to electromagnetism. You know the main mechanisms at work, but that does not mean you can study all the processes. Sometimes it's just that the sheer size of the mathematical model itself is basically impossible to study without a computer. Oftentimes, though, it's the inadequate formulation of a model that doesn't allow you to simulate it. A good simulation is an immensely useful tool. There are phenomenons which you know and can simulate, but you cannot easily measure their parameters while they are happening (e.g. you risk disrupting the phenomenon because of your measurement installation). I imagine this is even more so for chemists. Real-life example from my own research: we worked on tools that helped engineers who designed really high-frequency ICs (think tens of GHz) study things like cross-talk through the substrate. The mechanism itself is basically well-understood, but save for really, really simple structures that are nothing like those in an IC, you can't solve that by hand. Of course, ours were modest achievements, but the point is that this kind of research can open new gates and shouldn't be considered "second-rate".
blumkvist 13y ago
There are programs which allow you to input desirable qualities (smell, color, density, /non/conductor, molecule mass, stereo orientation to name a few, very basic ones) and it will make computations and it will give you possible compounds. Also software in chemistry can be used to simulate reactions and processes, which can take years to analyze with conventional methods(if at all possible), like folding protein chains.
- varelse 13y ago
  Actually, Vijay Pande's lab has been "folding" proteins in hours to days for years now by massively parallelizing the trajectories: http://en.wikipedia.org/wiki/Markov_chain_Monte_Carlo http://en.wikipedia.org/wiki/Markov_chain_Monte_Carlo Similarly, David Baker's lab has focused on producing the folded conformations of proteins in hours to days using simplified models that are designed for that task: http://boinc.bakerlab.org/rosetta/ http://boinc.bakerlab.org/rosetta/
deleted 13y ago
[deleted]
shiven 13y ago
You are thinking about reactions as written out in a chemistry textbook. Those representations tell you about the reactants, products and maybe a few other details like catalysts, solvents and temperature. However, none of it explains the mechanism at the quantum or atomic level. Simulating the reaction with specialized software enables you to 'calculate' additional data points, such as, free energy, enthalpy and entropy among others, using 'molecular dynamics' (which 'solves' Classical and Quantum Mechanics equations for a given system and is extremely essential to understand movement of different parts of a molecule and their interaction with surrounding atoms to build a more complete picture of 'how' a reaction proceeds). Today is a great day for computational chemistry. It is good to see the detailed Nobel announcement acknowledge other stalwarts of the field like Peter Kollman (who created AMBER, a package similar to CHARMm by Karplus et al). I have no doubt that Kollman would have received this prize had he been alive today.
- raverbashing 13y ago
  Exactly Chemistry is applied physics. Chemistry answers that H2 and O2 can be joined to form water under certain conditions, but doesn't answer the "Whys" Physics answers that. And the answer goes around orbitals, energy states, electrons, etc.
  - aristomc 13y ago
    "Chemistry answers that H2 and O2 can be joined to form water under certain conditions, but doesn't answer the whys". Chemistry does answer the whys beyond product yields, why certain elements react is vastly covered throughout organic, inorganic & physical chemistry . It is the basis of these sub-fields, and how this is determined is looking at orbitals, energy states etc...
    - raverbashing 13y ago
      Yes, there's an overlap of knowledge So, Pauli's exclusion principle is Physics or Chemistry? I'd say it's "both".
sp332 13y ago
You can simulate the reaction at a quantum-mechanical level at sub-nanosecond timesteps. That gives you a lot of information that you couldn't get from a test tube!
- varelse 13y ago
  OTOH you can't get sufficient sampling on anything but the smallest systems to make any sort of dynamic prediction about it. Not to mention the approximations that were made during the choice of basis sets for the atomic orbitals and how one decides to handle the configuration interaction. TLDR: Approximations are everywhere, make sure you work that into your conclusions.
- Xcelerate 13y ago
  I'll clarify that when he says sub-nanosecond timesteps, he means way sub-nanoscale timesteps. Femtosecond timesteps are used at the molecular dynamics level. Even smaller ones are used at the QM level.

dcc1 13y ago

lol @ title

timr 13y ago

Wow. I'm floored that computational structural biology work is getting a Nobel. I spent a lot of time reading their papers in grad school...they're totally foundational for the field, but the field is still really young: Martin Karplus' group is behind CHARMM (http://www.charmm.org http://www.charmm.org), which was the first(?) molecular dynamics package (you can think of it as a precursor to folding@home, though it's still under active development, so that isn't a totally fair statement). Michael Levitt has done a bunch of things, with no one big software package, but he was one of the earliest people trying to do ab initio protein structure prediction. He was also one of the first people to really start categorizing protein structure in a way that allowed for computational modeling -- back in the 70s and early 80s. Arieh Warshel is probably best known for bridging the gap between quantum mechanics and the (relatively quick-and-dirty) molecular mechanics work. He's done a whole bunch of work modeling enzymatic reactions, coming up with better electrostatic models, and other things where quantum mechanics does a good job, but is way too slow to be used on giant molecules like proteins.

alexholehouse 13y ago
Don't forget Karplus' colossal contribution to NMR
- dnautics 13y ago
  yeah, I'd say that is way more important to science. I have never used and never would use CHARMM, Karplus' J-coupling values - indispensable.
- timr 13y ago
  I had a whole other paragraph about that, but took it out because I figured that most people on HN wouldn't even know what NMR is, let alone NMR structure prediction. These guys have collectively done so much stuff that it's impossible to give a fair accounting of it all in a brief post.
bbgm 13y ago
Yes, but I am also not surprised given this is pretty fundamental work, even if it hasn't quite hit the sort of revolutionary goals many of us hoped for. If Peter Kollman had been alive, I suspect he would have shared this Nobel. This Nobel is hits very close to home. Much of my PhD work was done in CHARMM and I come from the Karplus lineage, and at one point in time I had pretty much read every paper Levitt and Warshel had ever written.

fireismyflag 13y ago

I initialy read it as "Chemistry Nobel Prize awarded to chemist's computer"... Makes me wonder if that will ever happen.

jnazario 13y ago

this is pretty awesome. in grad school in the 90s i was exploring a lot of this very early on, very few people around me were there to help and that's ultimately how i got involved using Linux and other FLOSS, then sysadmin, security work and now what i do in computer security research. very glad to see this prize granted for this line of work as it truly was a leap forward for the study of chemistry.

alexholehouse 13y ago

I'm somewhat surprised that Warshel was included instead of Berni Alder, as a more self-consistent group of scientists from a field point of view, and given Alder is largely seen as the father of MD.

selimthegrim 13y ago
Well then why not Ceperley too, as they helped straighten out some problems at the core of LDA? I think the Nobel committee wanted to keep the focus on biochem.
- alexholehouse 13y ago
  Agreed - that's the conclusion I came to too after posting. Still, I'd imagine Harold Scheraga and Andy McCammon are (justifiably) a little sore this morning...

mizanrahman 13y ago

health sector has more scope now to update their process and techniques. I think they should totally rethink their existing methodologies with the power of computation

varelse 13y ago
They are. But the previous generation of scientists came of age when Molecular Dynamics was a disappointing tool because of limitations in the Newtonian models and the lack of computational firepower to do sufficient sampling. The latter has been addressed by a combination of Moore's Law and the ongoing migration of molecular dynamics codebases to GPUs, but the former issue remains - a Newtonian approximation to quantum chemistry. What's surprising is how much one can get out of these simple models despite these limitations, something that was echoed back in 1976 by one of Michael Levitt's papers that led to today's Nobel Prize: http://csb.stanford.edu/levitt/Levitt_JMB76_Simplified_representation.pdf http://csb.stanford.edu/levitt/Levitt_JMB76_Simplified_repre...
- selimthegrim 13y ago
  There are very deep reasons for this - the Born-Oppenheimer approximation, a central simplifying assumption, imposes some constraints on the system that make it easier to model with (semi)classical dynamics, even when you marry it with modern techniques such as DFT. Kieron Burke has a nice take on the matter. http://www.tddft.org/TDDFT2008/talks/KB.pdf http://www.tddft.org/TDDFT2008/talks/KB.pdf see also http://www-fourier.ujf-grenoble.fr/~joye/simon2006.pdf http://www-fourier.ujf-grenoble.fr/~joye/simon2006.pdf, esp. its ref. 93

Xcelerate 13y ago

This is so cool! This is the kind of research I do: molecular dynamics and quantum mechanical simulation. I'm not nearly as good at it as the winners of this prize though haha. I'm glad to see computational research is becoming more popular and accepted. There's a (quickly diminishing) subset of scientists who think computational work is too theoretical, inaccurate, and inapplicable to real-life. This was the case when the field was developed, but it is no longer true. The exponentially increasing computational power is allowing discoveries that simply can not be performed experimentally because laboratory technology just isn't advanced or capable enough. Who needs to actually study reality if you can just simulate what you need -- and the end result is the same? I'm not sure many people know this, but our understanding of the laws of physics is advanced enough nowadays to describe almost perfectly everything we observe in everyday life. (Exceptions include things like quantum gravity which don't really matter [ducks to avoid physicists]). The problem is that if you want to simulate these laws, it requires a lot of computational power. Brute-force approaches are simply ineffective and so simplifications and clever techniques must be developed to reduce the computational effort while giving increasingly accurate results. I think it's the combination of improving computational resources and improving simulation algorithms that are really driving this field.

dnautics 13y ago
hey Xcelerate - I'm looking for someone to do some delta-Hf calculations on some "theoretical molecules" for me. By theoretical molecules, I mean, molecules that are very likely able to be made, but needs an assessment of "whether or not it's worth it". Is that something you can do, and would be interested in putting on ArXiV?
- pa5tabear 13y ago
  What data do you have? Do you know the mechanisms? We calculated heats of formation in our chemical thermodynamics course, but we were always given ample data, and we knew what we were trying to calculate.
  - selimthegrim 13y ago