Hacker News Reader

Comment by deletes | Hacker News Reader

To correctly model a cell you would need to simulate every atom and there are about 10^11 to 10^14 (!) of them in a single cell.

I think an interesting number would be how many atoms does it take to simulate one atom reasonably well. Then you could get correct results for some ( really ) small biological functions.

View on HN

Usually people modeling cells don't consider molecular dynamics, they consider concentrations of proteins, ions, and metabolites. A full MD simulation would obviously be superior, but useful predictions could be made without it.

It's hard to say which is the better approach. On the one hand you have MD from which you could technically build an accurate model "from scratch", folding all of your own proteins as part of the simulation, but it is exceedingly expensive to do that. On the other hand, you have a model built at the level of biochemical reactions and molecular biology, which is computationally feasible, but then you don't have enough information from bench work to flesh it out.

It depends what you mean by "full MD" too. That term can cover a multitude of sins. Truly accurate MD would be even more computationally expensive.

I used to do explicit MD with waters, etc, the whole shebang.

Massive waste of cycles. Never gonna make a useful prediction.

Reduced representations that contain the minimum of complexity to express the phenomena of interest are far more useful.

Your point is valid, but many people are trying to "correctly model a cell" without making a total atomistic simulation (which is clearly not going to happen any time soon). It's all about what questions you're looking to ask of a model.

What would you get from simulating both hydrogen atoms and the oxygen atom that you wouldn't get from simulating plain old water? The vast majority of a cell is just water, seems like you could cut your complexity in half with that abstraction.

I'm no molecular biologist, so i'll happily agree if you say there are some fraction of water molecules broken down, or formed by various cellular processes, but that must be a tiny fraction of the total, and could just be special cased.

It just seems like you're willfully ignoring everything physics has to say about how the universe works so you can get a big number for your calculation.

How would you plan on simulating all the variety of states, reactions and solutions involving plain old water without worrying about hydrogen and oxygen atoms?

Again, i would assert that a cell is 70% water. some tiny fraction of water that's actually used in a reaction would just be special cased, and modeled independently.

My understanding of "solution" is stuff floating in water. If there's some value in breaking out each atom, i'm all for it, but i kind of suspect the spherical cow is good enough in that case.

Even if i'm wrong there, each atom would introduce at least 6 degrees of freedom. IIRC, water is slightly polarized, and that's likely relevant to at least some reactions. Replacing the 18 degrees of freedom with 6 to represent a rigid water, or perhaps 10 or so to represent a flexible version, modeling as the molecule will dramatically lower complexity.

"My understanding of "solution" is stuff floating in water."

In that case, don't even bother with trying to work out what it would take to mathematically model biochemistry yet. Go study some basic physics and chemistry for a few years instead.

Ah yes, i called out water specifically and therefore i am an idiot. Mia Culpa. Best of luck with your simulation, i'm sure that individual atom model will work out great.

I don't know if you are an idiot, however you appear to have not even the slightest bit of technical understanding of the subject you are offering opinions on.

I am not attempting to be insulting, I am attempting to point out to you that you need to go and learn a hell of a lot more about the sciences than you seem to know at the moment if you are going to have any sort of productive discussion about the technical aspects of modelling biochemistry.

Just to scratch the surface of how complex water is, I suggest taking a look at this wikipedia article:

http://en.wikipedia.org/wiki/Properties_of_water

Note that cells are in fact completely packed- everything is grinding against everything else. THere's water there, but it's not a bunch of free solutes.

The interior of a cell does not follow solution dynamics at all in the way that you would like for it to, and this is why:

http://mgl.scripps.edu/people/goodsell/illustration/mycoplas...

That is an absolutely awesome illustration.

check out "macrophage and bacterium", by the same guy. All of the shapes of the proteins are informed by their crystal structures. The concentrations of them in the cell/plasma are also informed by known data about those environments.

That is a beautiful picture.

I don't understand why it's easier to simulate each individual atom than it is to simulate things with structure. I would assume a simulation would regard the long yellow strands of dna as dna rather than the component parts.

I'm used to a world where having structure implies constraints. With constraints, simulation can avoid a bunch of special cases and is therefore faster. I find foobarbazqux's approach of simulating each atom upsetting. But that's ok. You guys seem to think it's the way to go, and you all get results. shrug

-edit-

I don't think simulating water is easy, but i believe it's likely easier to simulate water than it is to simulate all possible states of the constituant atoms.

yeah, i don't think simulating each atom will work either. I'm not sure physics-based constraints at all is correct, and that maybe we need to try to generate heuristic constraints and then try to justify those heuristics using physics later.

At an atomic level, water plays critical roles in very small quantities and understanding these role requires detailed simulations. See this recent paper [1] for an example of how water molecules affect potassium channel inactivation, a key process in cardiac electrophysiology and other areas.

That's not to say that you can't get useful results by treating solvent as a continuum (or even ignoring it entirely), they'll just have a different kind of explanatory power.

[1] http://www.sciencedaily.com/releases/2013/07/130728134055.ht...

Aren't you modeling a subset of the universe at that level? Isn't a model supposed to provide a higher level understanding/abstraction?

Atom is still an abstraction of sub particles ( that may be made of even lower ones, we don't know ) and their physical interactions so i think it is a model. And a reasonably good one.

In cases where qualitative meaning is nontrivial, you don't know 100% what is going on, it is nevertheless possible to implement parametric studies for some target parameter.

Reply on news.ycombinator.com