[HN Gopher] Simulation of a 2B-atom cell that metabolizes and gr...
___________________________________________________________________
Simulation of a 2B-atom cell that metabolizes and grows like a
living cell
Author : jonbaer
Score : 239 points
Date : 2022-01-28 12:39 UTC (10 hours ago)
(HTM) web link (blogs.nvidia.com)
(TXT) w3m dump (blogs.nvidia.com)
| Jeff_Brown wrote:
| I wish they detailed how independent the simulated processes
| really are, and what sorts of dynamics are lost by not
| considering the atomic level.
| capableweb wrote:
| It seems that the researchers did use NVIDIA GPUs to perform the
| work, but it's not clear what sets the GPUs apart from others and
| why this research wouldn't be possible without NVIDIA's GPUs, as
| the article title and body implies.
| CoastalCoder wrote:
| Can someone comment on the legality of a 3rd party providing an
| unauthorized implemention of the CUDA API?
|
| I would think that Oracle's loss of a similar lawsuit with Java
| would be related.
| my123 wrote:
| > Can someone comment on the legality of a 3rd party
| providing an unauthorized implemention of the CUDA API?
|
| NVIDIA said that they would be fine with it in the past, and
| ROCm HIP is just a (bad) CUDA API clone.
| jabbany wrote:
| Interesting question. Press article aside, GPGPU applications
| like scientific compute, ML etc. have all mostly gravitated to
| Nvidia / CUDA.
|
| Not working in this space, I'm curious why this is the case. Is
| there something inherently better about CUDA? Or is it that
| Nvidia's performance is somehow better for these tasks? Or
| maybe something else?
| mattkrause wrote:
| The products are good, but NVidia also cleverly bootstrapped
| a whole ecosystem around them.
|
| One of the other posts mentions 2014 as a turning point. At
| that time, GPGPU stuff was entering the (scientific)
| mainstream and NVidia was all over academia, convincing
| people to try it out in their research. They handed out demo
| accounts on boxes with beefy GPUs, and ran an extremely
| generous hardware grant proposal. There was tons of (free)
| training available: online CUDA MOOCs and in-person training
| sessions. The first-party tools were pretty decent. As a
| result, people built a lot of stuff using CUDA. Others,
| wanting to use those programs, basically had to buy NVidia.
| Lather, rinse, repeat.
|
| This is in stark contrast to the other "accelerator" vendors.
| Around the same time, I looked into using Intel Xenon Phi and
| they were way less aggressive: "here are some benchmarks,
| here's how it works, your institution has one or two
| _somewhere_ if you want to contact them and try it out." As
| for OpenCL...crickets. I don't even remember any AMD events,
| and the very broad standard made it hard to figure out what
| would work /work well and you might end up needing to port it
| too!
| jjoonathan wrote:
| AMD's GPU OpenCL wasn't just not marketed, it was also a
| bad product, even for relatively tame scientific purposes,
| even when AMD made loud, repeated statements to the
| contrary. Hopefully now that AMD has money they can do
| better.
|
| I'm sure that NVidia's ecosystem building played a role (I
| remember events in 2009 and books before that), perhaps
| even a big role, but it wasn't the only factor. I paid a
| steep price in 2014 and 2016 for incorrectly assuming that
| it was.
| carlmr wrote:
| From my cursory knowledge of the topic, there are competitors
| like ROCm, but CUDA was the first that had a useable solution
| here. Also last time I checked ROCm doesn't have broad
| support on consumer cards, which makes it harder for people
| to try it out at home.
|
| But it seems ROCm is getting better and it has tensorflow and
| pytorch support, so there's reasons to be hopeful to see some
| competition here.
| naavis wrote:
| NVIDIA provides tools that just mostly do not exist for other
| GPUs, making it easier to build on CUDA instead of something
| else.
| hiptobecubic wrote:
| Absolutely this. When cuda was first making headway it was
| the only thing even remotely close to a "developer
| environment" and made things significantly easier than any
| of the alternatives.
|
| It might be different now, but at that time, many of the
| users were not computer scientists, they were scientists
| with computers. Having an easier to use programming model
| and decent debugging tools means publishing more results,
| more quickly.
| jjoonathan wrote:
| Back in 2014 or so I made the unfortunate mistake of buying
| AMD cards with the thought that I'd just use OpenCL. I knew
| that some codes wouldn't run, but I had catalogued the ones I
| really cared about and thought I was up for the challenge. I
| was so, so wrong.
|
| First of all, software that advertised OpenCL or AMD
| compatibility often worked poorly or not at all in that mode.
| Adobe creative suite just rendered solid black outputs
| whenever acceleration was enabled and forums revealed that it
| had been that way for years and nobody cared to fix it.
| Blender supported OpenCL for a while, but it was slower than
| CPU rendering and for a sticky reason (nvidia did the work to
| support big kernels with heavy branching and AMD didn't).
| Ironically, OpenCL mode had decent performance but only if
| you used it on an nvidia card.
|
| The situation was even worse in scientific codes, where
| "OpenCL version" typically meant "a half-finished blob of
| code that was abandoned before ever becoming functional, let
| alone anywhere near feature-parity."
|
| I quickly learned why this was the case: the OpenCL tooling
| and drivers weren't just a little behind their CUDA
| counterparts in terms of features, they were almost unusably
| bad. For instance, the OpenCL drivers didn't do memory (or
| other context object?) cleanup, so if your program was less
| than perfect you would be headed for a hard crash every few
| runs. Debugging never worked -- hard crashes all around.
| Basic examples didn't compile, documentation was scattered,
| and at the end of the day, it was also leagues behind CUDA in
| terms of features.
|
| After months of putting up with this, I finally bit the
| bullet, sold my AMD card, bought an NVidia card, ate the
| spread, the shipping, the eBay fees, and the green tax
| itself. It hurt, but it meant I was able to start shipping
| code.
|
| I'm a stubborn bastard so I didn't learn my lesson and
| repeated this process two years later on the next generation
| of cards. The second time, the lesson stuck.
| Tenoke wrote:
| Most likely because the software they use uses CUDA.
| capableweb wrote:
| I know that CUDA is faster than OpenCL for many tasks, but is
| there something that is not possible to achieve in OpenCL but
| possible in CUDA?
| belval wrote:
| > is there something that is not possible to achieve in
| OpenCL but possible in CUDA
|
| Developing fast... OpenCL is much harder to learn than
| CUDA. Take someone who did some programming classes,
| explain how CUDA works and they'll probably get somewhere.
| Do the same thing with OpenCL and they'll probably quit.
| TomVDB wrote:
| I'm subscribed to some CUDA email list with weekly updates.
|
| One thing that strikes me is how it evolves with new
| features. Not just higher level libraries, but also more
| fundamental, low level stuff, such as virtual memory,
| standard memory models, c++ libraries, new compilers,
| communication with other GPUs, launching dependent kernels,
| etc.
|
| At their core, OpenCL and CUDA both enable running parallel
| computing algorithms on a GPU, but CUDA strikes me as much
| more advanced in terms of peripheral features.
|
| Every few years, I think about writing a CUDA program (it
| never actually happens), and investigate how to do things,
| and it's interesting how the old ways of doing things has
| been superseded by better ways.
|
| None of this should be surprising. As I understand it,
| OpenCL has been put on life support by the industry in
| general for years now.
| 4gotunameagain wrote:
| If you ever need to reap the benefits of CUDA & GPU
| computations without getting into the details, check out
| JAX by our corporate overlords(tm)
| (https://github.com/google/jax), it has a NumPy like
| syntax and super fast to get started
| p1esk wrote:
| Why would you suggest JAX? CuPy seems like an obvious
| choice here (simpler and a lot more mature). Jax is only
| needed if you want automatic differentiation.
| Cthulhu_ wrote:
| Possibly, but that's not really the point, the article is
| part marketing push from nvidia for their HPC department.
| capableweb wrote:
| > but that's not really the point
|
| That's what I thought as well, so the title on the
| website ("NVIDIA GPUs Enable Simulation of a Living
| Cell") is not really truthful then.
| Symmetry wrote:
| My understanding is that CUDA has a lot of optimized
| libraries for common tasks, think BLAS, that don't
| currently exist in OpenCL/Vulkan Compute.
| 01100011 wrote:
| Nvidia is pushing vertical integration hard. There are all
| sorts of libraries from Nvidia which build on top of CUDA, from
| simple cuBLAS to smart cities, autonomous driving, robotics and
| 5G.
|
| They also provide acceleration of open source libraries like
| GROMACS, used for molecular dynamics simulation.
| erwincoumans wrote:
| The fine grain parallelism of this simulation suits the GPU
| well. It would be possible on multicore CPUs, but possibly
| slower.
| tmearnest wrote:
| There are two main reasons to take advantage of the Gpu in
| lattice microbes. It can simulate the stochastic chemical
| reaction and diffusion dynamics in parallel: one thread per
| voxel. For instance, an E. coli sized cell would have ~40000
| voxels. It's not quite embarrassing parallel, but close.
| Second, the simulation is totally memory bound so we can take
| advantage of fast gpu memory. The decision to use CUDA over
| OpenCL was made in like 2009 or so. Things have changed a lot
| since then. I don't think anyone has the time or interest to
| port it over, unfortunately.
| Gehoti wrote:
| I'm much more aware of slot of things research is doing with
| Nvidia.
|
| Due to cuda, tools, SDKs etc Nvidia is providing.
|
| I'm not aware of anything similar at any other GPU company
| neom wrote:
| I don't see in the article why this is useful or what is it used
| for?
| joejoesvk wrote:
| i don't even know where to start. you could simulate one cell,
| then two cells then 4..suddenly you could have an
| organisms...hell you could see organism that could have lived
| on earth.
|
| maybe it'll one day help with cancer research.
| JabavuAdams wrote:
| It's generally not possible to see where everything is in an
| actual cell, in realtime, due to the sizes of the components.
| So most of molecular biology relies on very clever lab
| techniques to indirectly infer what cells are making and doing.
|
| Cells are like little cities in terms of the complexity of
| their biochemistry. We want to ask questions like "How does
| this cell respond to this chemical/drug/change in environment."
|
| Imagine trying to understand in detail the gun crime epidemic
| in a city, if you can only see objects larger than 100 m on a
| side. You wouldn't see people, cars, or many buildings.
|
| We want to be able to understand, explain, predict, and control
| cellular process, but so far we have to be quite indirect.
| Understanding these things at a mechanistic level, in realtime
| would revolutionize our ability to understand, repair, and
| build biological systems.
| JabavuAdams wrote:
| For instance, the cartoon version of DNA that is presented to
| even lower-year biology undergraduates is of linearized
| strands. But of course, it's really all spooled and tangled and
| crunched up into the nucleus of cells. Note that the cell they
| simulated is of a prokaryote (no nucleus, much simpler cellular
| processes than e.g. a mammal cell). About 1-2% of our genes
| make proteins, although the proportion is much larger in
| single-celled organisms (less redundancy in the genome, no
| splicing, etc.) So when you hear that e.g. genes turn on or
| off, this is not a switch. It's literally some sections of DNA
| being unwound, and large complexes of mutually interacting
| molecules probabilistically glomming on and off the DNA. The
| actual 3d layout of this DNA "ramen" matters to e.g. bring
| promoter regions of genes close to the actual genes they
| control.
|
| So basically, we have a schematic-level understanding of
| cellular processes, but to see the actual 3D interactions in
| realtime would be extremely illuminating.
| JabavuAdams wrote:
| I should say that this work is not simulating things at this
| detail. Instead, it's more like a biophysical model of a
| bunch of chemical reactions with rate information. It
| probably boils down to a big system of coupled differential
| equations, at different timescales. So, it's a statistical
| level of detail, but still very informative.
| madhato wrote:
| Its simple really. First you simulate a single cell, then a
| sperm and an egg cell. Then you simulate a virtual a world of
| virtual captive humans to do our work for us without payment.
| barrenko wrote:
| Devs, the prequel.
| amelius wrote:
| A two-billion atom cell ... isn't that a bit small for a cell?
| wcoenen wrote:
| Yes. The cell was first created in the real world as part of
| research about the minimal set of genes required for life.[1]
| It is known as "JCVI-syn3.0" or "Mycoplasma laboratorium".'[2]
|
| Still amazing that it can now be fully simulated "in silico".
|
| [1] https://www.science.org/doi/10.1126/science.aad6253
|
| [2] https://en.wikipedia.org/wiki/Mycoplasma_laboratorium
| Traubenfuchs wrote:
| It says
|
| "In this new organism, the number of genes can only be pared
| down to 473, 149 of which have functions that are completely
| unknown."
|
| But if we now can simulate this cell completely, shouldn't it
| be easy to figure out what those genes are doing? Just start
| the simulation with them knocked out.
| WJW wrote:
| Presumably if the number of genes cannot be pared down
| below 473, it dies very quickly if one of the 149 genes is
| knocked out. But "it doesn't work without it" is not a very
| satisfactory answer to "what does it do".
| amelius wrote:
| Yes, this is similar to opening a radio and saying "I
| don't know what this transistor does; let's take it out
| and see what the radio does".
| dekhn wrote:
| See also "Can a biologist fix a radio"
| https://www.cell.com/cancer-
| cell/pdf/S1535-6108(02)00133-2.p... "Doug & Bill"(http://
| www2.biology.ualberta.ca/locke.hp/dougandbill.htm) "Could
| a neuroscientist understand a microprocessor"? https://jo
| urnals.plos.org/ploscompbiol/article?id=10.1371/jo...
|
| The funny thing is if you read the history of Feynman and
| others, most of them grew up opening up radios and
| learning how they worked by removing things. fixing them.
| It's a very common theme (sort of falls off post-
| transistor tho). I opened up radios as a kid, tried to
| figure out what parts did what, and eventually gave up.
| breck wrote:
| That is a great read. Thanks :)
| Jeff_Brown wrote:
| Before attempting to crack the copy-protection on a game,
| one might think something similar.
| quickthrower2 wrote:
| Valgrind that cell!
| vital101 wrote:
| The article mentions that they use minimal cells. "Minimal
| cells are simpler than naturally occurring ones, making them
| easier to recreate digitally."
| Jeff_Brown wrote:
| How much emergent behavior arises from the model? The only
| passage I see describing any of it is this one:
|
| > The model showed that the cell dedicated most of its energy to
| transporting molecules across the cell membrane, which fits its
| profile as a parasitic cell.
|
| Whether it mimics the behavior of real cells seems like the right
| test. We'll never be able to get it to parallel the outcome of a
| real system, thanks to chaos theory. But if it does lots of
| things that real cells do -- eating, immune system battles,
| reproduction -- we should be pretty happy.
| vasili111 wrote:
| Is this simulation on the atomic level with full all interatomic
| physics processes simulation or there were made some
| simplifications?
|
| All interatomic interactions are simulated separately for each
| atom or they made statistical estimations and used some
| assumptions? Those two are absolutely two different types of
| simulation.
| alpineidyll3 wrote:
| Absolutely definitely not. It's not even possible to simulate a
| single protein-molecule interaction to an accuracy such that
| reaction rates are reproduced at room temperature. Small
| effects such as the quantum nature of H-motion prevent this
| from happening with present computational resources.
|
| This research is something like a pixar movie, or one of those
| blender demos with a lot of balls :P
| perihelions wrote:
| > _" full all interatomic physics"_
|
| It's certainly not that -- that's a hideously difficult
| algorithm with exponential complexity.
|
| https://en.wikipedia.org/wiki/Full_configuration_interaction
| sseagull wrote:
| It's worse than exponential, it's factorial :)
| unemphysbro wrote:
| verlet list is the standard algo used to reduce the
| complexity in the number of interatomic calculations
|
| https://en.wikipedia.org/wiki/Verlet_list
| dekhn wrote:
| that's old tech, these days it's usually some sort of PPPM
| (particle-particle particle-mesh) which parallelizes
| better.
|
| But that's for classical simulations. Full configuration
| interaction is effecftively computing the schrodinger
| equation at unlimited precision, in principle if you could
| scale it up you could compute any molecular property
| desired, assuming QM is an accurate model for reality.
| unemphysbro wrote:
| p3m, well pme, is exactly what we used for our
| calculations ;)
|
| i never did any qm work beyond basic parameterization
|
| i'm guessing you are/were also computational physics guy
| :)
| dekhn wrote:
| I was a computational biologist for many years, which
| included a bunch of biophysics. I did extensive work with
| PME about 20 years ago, on supercomputers. It's a pretty
| neat technique
| (https://en.wikipedia.org/wiki/Ewald_summation), once you
| wrap your head around it!
| unemphysbro wrote:
| yup, we used PME for non-bonded calculations in our
| simulations and to calculate things like electric
| potentials. I finished a biophysics phd back in 2020 and
| focused mainly on fluid flow.
|
| Pretty cool, what're you up to now?
| gfd wrote:
| In theory, I don't think there's such a thing as simulation
| without simplifications. The world seems to be continuous but
| our computers are discrete. There's a small set of things we
| know how to solve exactly with math but in general we have no
| ways to deal infinity. Any given variable you're calculating
| will be truncated at 32 or 64 bits when in reality they have an
| infinite number of digits, changing at continuous timesteps,
| interacting with every other atom in the universe.
|
| In practice, none of this matters though and we can still get
| very useful results at the resolution we care about.
| merely-unlikely wrote:
| There's this concept that causation moves at the speed of
| light. When I first heard that, it sounded very much like a
| fixed refresh rate to me. Or maybe the "real world" is just
| another simulation
| Filligree wrote:
| It does if you put it _that_ way, but another way of
| putting is that spacetime is hyperbolic (...well,
| lorentzian), and all (lightspeed) interactions are zero-
| ranged in 4D.
|
| As in, photons that leave the surface of the sun _always_
| strike those specific points in space-time which are at a
| zero spacetime interval from said surface. If you take the
| described geometry seriously, then "spacetime interval" is
| just the square of the physical distance between the
| events.
|
| (And any FTL path has a negative spacetime interval. If
| that's still the square of the distance, then I think we
| can confidently state that FTL is imaginary.)
| qboltz wrote:
| All simulations have to make the Born-Oppenheimer
| approximation, nuclei have to be treated as frozen, otherwise
| electrons don't have a reference point.
|
| There will never be true knowledge of both a particle's
| location and momentum a la uncertainty principle, and will
| always have to be estimated.
| chermi wrote:
| What? This is simply untrue.
| drdeca wrote:
| But, for a system of two quantum particles which interact
| according to a central potential, you can express this
| using two quantum non-interacting particles one of which
| corresponds to the center of mass of the two, and the other
| of which corresponds to the relative position, I think?
|
| And, like, there is still uncertainty about the position of
| the "center of mass" pretend particle, as well as for the
| position of the "displacement" pretend particle.
|
| (the operators describing these pretend particles can be
| constructed in terms of the operators describing the actual
| particles, and visa versa.)
|
| I don't know for sure if this works for many electrons
| around a nucleus, but I think it is rather likely that it
| should work as well.
|
| Main thing that seems unclear to me is what the mass of the
| pretend particles would be in the many electrons case. Oh,
| also, presumably the different pretend particles would be
| interacting in this case (though probably just the ones
| that don't correspond to the center of mass interacting
| with each-other, not interacting with the one that does
| represent the center of mass?)
|
| So, I'm not convinced of the "nuclei have to be treated as
| frozen, otherwise electrons don't have a reference point"
| claim.
| aeternum wrote:
| With a quantum computer could one theoretically input the
| super position of possible locations and momenta and run
| the simulation based on that?
| phkahler wrote:
| A simulation can have both.
| Tagbert wrote:
| Then is it an accurate simulation without the
| uncertainty?
| dekhn wrote:
| I doubt it makes sense to assume the unverise is continuous
| (I'm glad you said "seems"). In particular, space could be
| spatially quantized (say, around the planck length) or any
| number of other details.
|
| People have done simulations with quad precision (very slow)
| but very few terms in molecular dynamics would benefit from
| that. In fact, most variables in MD can be single precision,
| exceptt for certain terms like the virial.
| whatshisface wrote:
| All of our current theories are set in continuous
| spacetime. At the present, there's no reason to assume
| anything else.
| dekhn wrote:
| the issue is that there are no theories based on
| experimental evidence at very small scales. I agree that
| in most situations, it would be silly to violate this
| assumption, unless you were working on advanced physics
| experiments.
| jacquesm wrote:
| True, but we do not actually know this for sure. There is
| a (small) possibility that we are simply looking at this
| at a scale where all we see is macro effects. It would
| require the quanta to be much smaller than the Planck
| distance though.
| webmaven wrote:
| _> There is a (small) possibility that we are simply
| looking at this at a scale where all we see is macro
| effects. It would require the quanta to be much smaller
| than the Planck distance though._
|
| How much smaller?
| jacquesm wrote:
| Many orders of magnitude. How many? I do not know, I
| don't think anybody does.
|
| But photons resulting from the same event but with
| different energies arrive at detectors an appreciable
| distance away to all intents and purposes simultaneously,
| something that would not happen if spacetime were
| discrete at a level close to the Planck length. So it
| would have to be quite a big difference for an effect
| _not_ to show up as a difference in time-of-flight.
| feoren wrote:
| I wouldn't say that "all our current theories" are set in
| continuous spacetime. For example, Quantum chromodynamics
| is set in SU(3), an 8-dimensional group of rotation-like
| matrices. Electric charge is discrete, spin is discrete,
| electron orbitals are discrete. In fact position and
| momentum would seem to be the outlier if they were not
| also discrete. I hardly call that "no reason".
| whatshisface wrote:
| SU(3) is a continuous group.
| freemint wrote:
| Yeah but it is very much not in space time.
| whatshisface wrote:
| But it is. SU(3) is the group for swapping colors around.
| It still has spacetime.
| freemint wrote:
| You can Cartesian product it with space time, yes. But
| that is possible for any system.
| drdeca wrote:
| It is based on SU(3), but, does it really make sense to
| say that it isn't still set in spacetime? Like, quarks
| still have position operators, yes?
| mensetmanusman wrote:
| It's definitely fun to think about.
|
| If the universe is discrete, how does one voxel communicate
| to the neighboring voxel what to update without passage
| through 'stuff in between' that doesn't exist? Heh
|
| It seems physics is going the opposite way with infinite
| universes and multiple dimensions to smooth out this
| information transfer problem and make the discrete go away.
| javajosh wrote:
| As someone with keen interest in physics (and a bit of
| training) I find speculation about "discrete space"
| disquieting. It's the level of abstraction where
| intuition about space breaks down, and you have to be
| very careful. Remember that coordinate systems are short-
| hand for measurement. It's one thing to admit fundamental
| limits on measurement resolution, and quite another to
| say that space itself is quantized! Mostly I get around
| this by not thinking about it; most of these theories are
| only testable in atrocious and unattainable conditions,
| doing things like performing delicate QED experiments at
| the edge of a black hole.
|
| I don't think your "voxel" intuition can be right because
| it's a small jump from that to (re)introducing an
| absolute reference frame.
| joshmarlow wrote:
| > how does one voxel communicate to the neighboring voxel
| what to update without passage through 'stuff in between'
| that doesn't exist? Heh
|
| That kind of reminds me of the 'aether' that was once
| hypothesized as a medium of transmission for light and
| radio waves [0].
|
| Also, voxel's communicating sounds an awful lot like a
| higher-dimensioned cellular automata.
|
| [0] - https://en.wikipedia.org/wiki/Aether_theories
| Yajirobe wrote:
| Stephen Wolfram was right all along
| Frost1x wrote:
| It doesn't appear to be ab initio simulated (e.g. QED up) if
| that's what you're asking. They appear to swoop in at higher
| scales (molecular level) and simulate molecular interactions
| across "hundreds of molecular species" and "thousands of
| reactions."
|
| Apparently the interface between molecules uses the Chemical
| Master Equations (CME) and Reaction-Diffusion Master Equations
| (RDME) both of which I'm unfamiliar with:
| http://faculty.scs.illinois.edu/schulten/lm/download/lm23/Us...
| vasili111 wrote:
| For anyone who is wondering what QED is: Quantum
| electrodynamics (QED)
| https://en.wikipedia.org/wiki/Quantum_electrodynamics
| kingcharles wrote:
| Ah, should have realized when Quad Erat Demonstradum made
| no sense...!
| dahart wrote:
| Yes, this appears to be the underlying simulation software.
| Here's a home page link to the project as well:
| http://faculty.scs.illinois.edu/schulten/Software2.0.html
|
| "Lattice Microbes is a software package for efficiently
| sampling trajectories from the chemical and reaction-
| diffusion master equations (CME/RDME) on high performance
| computing (HPC) infrastructure using both exact and
| approximate methods."
| [deleted]
| marcosdumay wrote:
| The paper (well, the abstract) calls it "fully dynamical
| kinetic model".
|
| Or, in other words, it doesn't solve the Schrodinger equation
| at all, but uses well known solutions for parts of the
| molecules, and focuses on simulating how the molecules interact
| with one another using mostly classical dynamics.
| blix wrote:
| I do classical molecular dynamics simulations for a living,
| and I feel the model using in this paper is pretty
| dramatically different than what would typically be described
| as classical dynamics. 2B atoms would be absolutely insane
| for any sort of simulation that resolves forces between atoms
| of even groups of atoms, especially in organic systems.
|
| As far as I can tell from their model, molecules don't
| interact with each other ~at all~ through classical dynamics.
| Rather, they define concentrations of various molecules on a
| voxel grid, assign diffusion coffecients for molecules and
| define reaction rates between each pair of molecules. Within
| each voxel, concentrations are assumed constant and evolve
| through a stochastic Monte-Carlo type simulation. Diffusion
| is solved as a system of ODEs.
|
| This is a cool large scale simulation using this method, but
| this is a far cry from an actual atomic-level simulation of a
| cell, even using the crude approximations of classical
| molecular dynamics. IMO it is kind of disingenuous for them
| to say 2B atoms simulation when atoms don't really exist in
| their model, but it's a press release so it should be
| expected.
| CorrectHorseBat wrote:
| Of course not, we can't even simulate how one protein folds.
| Cthulhu_ wrote:
| What does https://foldingathome.org/ do then? That's been
| going on for nearly two decades.
| echelon wrote:
| Simulating very expensive to compute protein dynamics.
| These aren't guaranteed solutions, but it's still useful
| information.
| vasili111 wrote:
| So, even one protein cannot be simulated as in real
| world?
| qboltz wrote:
| Not if you're going off of ab initio theory such as
| Hartee Fock, MP2, CC, etc. We're talking amounts of
| matrix multiplication that wouldn't be enough to finish
| calculating this decade, even if you had parallel access
| to all top 500 supercomputers, you get bigger than a
| single protein, it's beyond universal time scales with
| current implementations.
| dekhn wrote:
| Every time some computer scientist interviews me and
| shows off their O(n) knowledge (it's always an o(n)
| solution to a naive o(n**2) problem!) I mention that in
| the Real World, engineers routinely do O(n**7)
| calculations (n==number of basis functions) on tiny
| systems (up to about 50 atoms, maybe 100 now?) and if
| they'd like to help it would be nice to have better,
| faster approximations that are n**2 or better.
| Unfrotunately, the process of going from computer
| scientist to expert in QM is entirely nontrivial so most
| of them do ads ML instead
| dekhn wrote:
| A custom supercomputer dedicated to simulating folding
| proteins (two-state folders with nontrivial secondary and
| tertiary structure) from unfolded to correctly folded
| state using only classical force fields _probably_ could
| work, and DE Shaw has invested a lot of money in that
| idea: https://en.wikipedia.org/wiki/Anton_(computer)
|
| but, as I pointed out elsewhere, this would not be
| particularly helpful as it would use an enormous amount
| of resources to compute something we could probably
| approximate with a well-trained ML model.
|
| It also wouldn't address questions like biochemistry,
| enzymatic reactions, and probably wouldn't be able to
| probe the energetics of interactions accurately enough to
| do drug discovery.
| beecafe wrote:
| One single iron atom's electrons - 26 of them - contain
| more degrees of freedom than atoms in the solar system.
| JabavuAdams wrote:
| Even one atom of a heavier element cannot be simulated in
| the real, depending on what level of detail you want.
| Multi-atom simulations usually treat them as little non-
| quantum balls moving around in a force-field that may
| have been approximated from quantum mechanics.
| orangepurple wrote:
| Full list of achievements
| https://foldingathome.org/category/fah-achievements/?lng=en
|
| This is the only real update of the year:
| https://foldingathome.org/2022/01/03/2021-in-review-and-
| happ...
|
| SARS-CoV-2 has intricate mechanisms for initiating
| infection, immune evasion/suppression and replication that
| depend on the structure and dynamics of its constituent
| proteins. Many protein structures have been solved, but far
| less is known about their relevant conformational changes.
| To address this challenge, over a million citizen
| scientists banded together through the Folding@home
| distributed computing project to create the first exascale
| computer and simulate 0.1 seconds of the viral proteome.
| Our adaptive sampling simulations predict dramatic opening
| of the apo spike complex, far beyond that seen
| experimentally, explaining and predicting the existence of
| 'cryptic' epitopes. Different spike variants modulate the
| probabilities of open versus closed structures, balancing
| receptor binding and immune evasion. We also discover
| dramatic conformational changes across the proteome, which
| reveal over 50 'cryptic' pockets that expand targeting
| options for the design of antivirals. All data and models
| are freely available online, providing a quantitative
| structural atlas.
| dekhn wrote:
| Small proteins (one to two alpha helices) can now be
| routinely folded (that is, starting form a fully unfolded
| state, to getting stick in the minimum around the final
| structure) using ab initio simulations that last several
| multiples of the folding time.
|
| Larger proteins (a few alpha helices and beta sheets), the
| folding process can be studied if you start with structures
| near the native state.
|
| None of this means to say that we can routinely take any
| protein and fold it from unfolded state using simulations and
| expect any sort of accuracy for the final structure.
| qboltz wrote:
| When you say ab initio calculations, could you cite the
| level of theory? I think there could be some ambiguity
| given differences in scope.
| dekhn wrote:
| When I say ab initio I mean "classical newtonian force
| field with approximate classical terms derived from QM",
| AKA something like https://ambermd.org/AmberModels.php
|
| Other people use ab initio very differently (for example,
| since you said "level of theory" I think you mean basis
| set). I don't think something like QM levels of theory
| provide a great deal of value on top of classical (and at
| a significant computational cost), but I do like 6-31g*
| as a simple set.
|
| Other people use ab initio very differently. For example,
| CASP, the protein structure prediction, uses ab initio
| very loosely to me: "some level of classicial force
| field, not using any explicit constraints derived from
| homology or fragment similarity" which typically involves
| a really simplified or parameterized function (ROSETTA).
|
| Personally I don't think atomistic simulations of cells
| really provide a lot of extra value for the detail. I
| would isntead treat cell objects as centroids with mass
| and "agent properties" ("sticks to this other type of
| protein for ~1 microsecond"). A single ribosome is a
| single entity, even if in reality it's made up of 100
| proteins and RNAs, and the cell membrane is modelled as a
| stretchy sheet enclosing an incompressible liquid.
| blix wrote:
| I would not describe AMBER, or anything using a newtonian
| force field, as ab initio.
|
| In inorganic materials ab initio means you actually solve
| Schrodinger's equation (though obviously with aggressive
| simplifications e.g. Hartree-Fock).
| qboltz wrote:
| Level of theory as it relates to an-initio QM
| calculations usually indicates Hartee Fock, MP2 and so
| on, then the basis set gets specified after.
|
| I also agree that QM doesn't provide much for the cost at
| this scale, I just wish the term ab initio would be left
| to QM folks, as everything else is largely just the
| parameterization you mentioned.
| dekhn wrote:
| The systemn I work with, AMBER, explains how individual
| classical terms are derived: https://ambermd.org/tutorial
| s/advanced/tutorial1/section1.ht... which appears te be
| MP2/6-31g* (sorry, I never delved deeply into the QM
| parts). Once those terms are derived, along with various
| approximated charges (classical fields usually just treat
| any charge as point-centered on the nucleus, which isn't
| great for stuff like polarizable bonds), everything is
| purely classical springs and dihedrals and interatomic
| potentials based on distance.
|
| I am more than happy to use "ab initio" purely for QM,
| but unfortunately the term is used widely in protein
| folding and structure prediction. I've talked
| exdtensively with David Baker and John Moulton to get
| them to stop, but they won't.
| [deleted]
| intrasight wrote:
| Someone is simulating all of my cells - and yours too ;)
| CapsAdmin wrote:
| If this is true, there must be some species at some level of
| simulation who's not being simulated.
|
| I'm not sure if you're being real or not, but if you are, do
| you think the species running who made our simulation are also
| being simulated?
| webmaven wrote:
| _> If this is true, there must be some species at some level
| of simulation who 's not being simulated._
|
| You can't fool me, it's turtles all the way down!
|
| With that out of the way, I'll observe there is no reason
| that such a base layer of reality need bear any particular
| resemblance to ours except in the tautological sense that it
| would need to be Turing complete in order to be capable of
| hosting a simulation.
| CapsAdmin wrote:
| I agree that it would probably not resemble our universe. I
| would think it has to be a universe that's capable of
| simulating our universe without consuming all of the host
| universe's resources as it would need at least some sort of
| species that would want to simulate our universe. At least
| initially.
|
| I'm not sure what you (and other people) really mean when
| you say our universe is simulated.
|
| - Do you mean that the entire universe is simulated down to
| the planck level? - Do you think there's some sort of
| optimization going on? - Do you think it's done by a
| species that evolved to become curious to see what would
| happen if you simulate the universe (like us)?
|
| I can say that our universe is simulated too, but I have no
| idea if this simulation was made by someone or if it "just
| is".
|
| But if you believe the universe is a simulation in some
| host universe, then it must be possible to have a universe
| that "just is" / or is Turing complete as you put it.
| webmaven wrote:
| I mean that such a universe could be so different from
| ours that the idea of 'species' may not even be sensible.
|
| _> Do you mean that the entire universe is simulated
| down to the planck level?_
|
| Unspecified. Perhaps gross approximations are used unless
| an attempt is made to observe (internally or externally)
| more detail.
| CapsAdmin wrote:
| > I mean that such a universe could be so different from
| ours that the idea of 'species' may not even be sensible.
|
| Alright. I've heard people say they think our universe is
| being simulated because that's what we would do. For
| those who think that, the host universe is at least
| somewhat similar to us.
|
| > Unspecified. Perhaps gross approximations are used
| unless an attempt is made to observe (internally or
| externally) more detail.
|
| But if gross approximations are true, that reveals
| information about the host doesn't it? If they resort to
| approximations because they don't have enough resources,
| that tells us they must really want to do this for some
| reason. Did they want to create our simulation for fun?
| Out of desperation? Are we made for research purposes?
| All those questions point to something human-like in my
| opinion, and thus "species".
| svachalek wrote:
| Could be an Ouroboros, the entirety of existence being
| created from nothing in an enormous circular dependency. It
| sounds farcical but when you think about why the universe
| exists in the first place, it seems as good a reason as any.
| CapsAdmin wrote:
| > when you think about why the universe exists in the first
| place, it seems as good a reason as any.
|
| I think this sums up how I think. If any reason is as good
| as any then it's equally likely that our universe is not
| simulated and not an Ouroboros.
|
| It can be a lot of fun to speculate and think about though.
| VikingCoder wrote:
| How long did it take to simulate 20 minutes?
|
| Looks like one NVIDIA Titan V took 10 hours to do it, and one
| NVIDIA Tesla Volta V100 GPU took 8 hours to do it?
|
| Am I reading that right?
|
| So the NVIDIA Tesla Volta V100 is 24 times slower than real life?
| Pretty cool.
| Koshkin wrote:
| Generally speaking, this depends on the size (in terms of the
| number of constituents) of the piece of "real life" you are
| simulating.
| kingcharles wrote:
| The question is (again) how soon now until I can boot the "ROM"
| file of my DNA in an emulator?
| jacquesm wrote:
| This won't happen. Computationally inconceivable with all that
| we know at the moment.
| sydthrowaway wrote:
| This seems like the company that will dominate the 2020s. The
| time is ripe to join NVIDIA
| rsfern wrote:
| This is really cool, but I don't think it's an atomistic
| simulation so I'm not sure where the title is coming from.
|
| It seems to be some kind of a (truly impressive) kinetic model
|
| The paper in Cell is open access
| https://doi.org/10.1016/j.cell.2021.12.025
| fefe23 wrote:
| Nvidia GPUs enable nothing, because you can't buy any at
| reasonable prices.
| hiptobecubic wrote:
| "That place is so crowded that no one goes there anymore."
| HPsquared wrote:
| Leela: Did you drive much in the 20th century, Fry?
|
| Fry: Nobody in New York drove, there was too much traffic.
| jabbany wrote:
| This argument makes no sense. Consumer GPU pricing (which I'm
| assuming is what you're referring to) has very little to do
| with the pro market (industry, research etc.)
|
| The researchers are using things like the DGX or RTX A-series.
| These, while quite expensive, are not that unreasonable when it
| comes to pricing.
| pepemon wrote:
| An individual could afford computing power for such research
| activities (not exactly like this one, but e.g. for personal
| ML experiments) in 2018-2019 for an adequate price. You were
| able to buy 2 new RTX2080s for the today price of a used
| single unit. If you want to tinker and need GPU power today,
| your best option is to rent special datacenter-approved(tm)
| GPUs for the really expensive $/h. And you don't own anything
| afterwards (except if you bought GPU before the end of 2020).
| Does this make no sense? Is this how technological progress
| should work?
| freemint wrote:
| If you don't care if some rando who's machine you rented
| does see what you are doing vast.ai can be a good resource
| for GPU compute too.
| jabbany wrote:
| 2080s? With only 8GB of VRAM that's not even ECC backed?
|
| Even for ML model training back then, 8GB was on the small
| side (a lot of the research repos even had special
| parameter sets to allow running on consumer level VRAM
| GPUs). Also, for something like long running bio
| simulations, you'd probably want to be sure that your
| memory bits aren't being flipped by other sources -- the
| extra upfront cost is well worth preventing potentially
| wrong research results...
|
| Nvidia consumer products have been a better value
| proposition in the past for sure. But they've always done
| market segmentation. It's not merely a matter of
| "datacenter-approved(tm) GPU" (though they do also do
| driver-based segmentation).
| lolive wrote:
| Apart from this article, do we have any visual representation [a
| CGI, may be] of the full activity inside a cell?
| unemphysbro wrote:
| vmd is a standard biological system simulation rendering
| software
| 01100011 wrote:
| I always appreciated the work of David Goodsell at UCSD:
| https://ccsb.scripps.edu/goodsell/
|
| He paints cell internals.
|
| I also like the Biovisions videos from Harvard:
|
| https://www.youtube.com/watch?v=VdmbpAo9JR4
| vasili111 wrote:
| We can't visualize what we do not know. Full activity inside
| cell is not known and we are pretty far from knowing that.
| lolive wrote:
| I have always been amazed by these 2D representations:
| https://www.digizyme.com/cst_landscapes.html
| Traubenfuchs wrote:
| All of this incomprehensible complexity just so our genes can
| compete against other genes in their mindless drive for
| survival. It's kind of sad.
| [deleted]
| jjoonathan wrote:
| Things really got out of hand after that first self-
| replicating gizmo, didn't they?
| lolive wrote:
| The boilerplate to make a double click with your mouse do
| something relevant is also completely mind blowing.
| #complexity
| dekhn wrote:
| one note- as lovely as those are, they don't make the point
| that everything in the cell (all the proteins, etc) is
| constantly grinding against each other (there's almost no
| room for water).
| maze-le wrote:
| That's fascinating, thanks for sharing!
| airstrike wrote:
| Now we just need to scale this by a mere 37,200,000,000,000x and
| we'll have simulated the entire human body!
| chroem- wrote:
| Moore's law suggests it will be possible in 90 years if the
| historical trend holds true.
| T-A wrote:
| https://www.cnet.com/tech/computing/moores-law-is-dead-
| nvidi...
| elil17 wrote:
| Price and energy use can still go down even if transistor
| density stays the same
| chroem- wrote:
| Luckily, there are other means of performing computation
| than just silicon transistors.
| [deleted]
| ajuc wrote:
| I think it has to reproduce to qualify.
| agentultra wrote:
| Permutation City, here we come.
|
| I wonder if Greg Egan had the foresight to predict this for the
| story or if he invented that part for narrative purposes.
| chinathrow wrote:
| When I was like 12 or so, I had a thought that if we can
| calculate everything, we could be living in a full blown
| simulation.
|
| To be honest, like 30y later, I still go back to that nagging
| thought _a lot_.
| afshin wrote:
| This idea has been formalized: https://www.simulation-
| argument.com/
| sva_ wrote:
| This idea has also existed for at least 200 years
|
| https://en.m.wikipedia.org/wiki/Laplace%27s_demon
| lelandfe wrote:
| https://en.wikipedia.org/wiki/Evil_demon
|
| Going further back to the 1600's, Descartes' idea of an
| evil demon deceiving one's mind with a perfect, fake
| reality made me think often of simulations in my
| undergrad philosophy classes
| dekhn wrote:
| I read that as a teenager, thought it sounded nice, went
| to grad school and did molecular dynamics simulations
| (like folding at home) for a decade, then went to google
| and built the world's largest simulation system
| (basically, the largest group of nodes running folding at
| home). Eventually we shut the system down because it was
| an inefficient way to predict protein structure and
| sample folding processes (although I got 3-4 excellent
| papers from it).
|
| The idea is great, it was a wonderful narrative to run my
| life for a while, but eventually, the more I learned, the
| more impractical using full atomistic simulations seem
| for solving any problem. It seems more likely we can
| train far more efficient networks that encapsulate all
| the salient rules of folding in a much smaller space, and
| use far less CPU time to produce useful results.
| sva_ wrote:
| Yeah, I think the idea of Laplace's Demon is mostly just
| useful to make a philosophical argument about whether or
| not the universe is deterministic, and it's implication
| on free will.
| dekhn wrote:
| I dunno, I wonder what Laplace would have made of the
| argument over the meaning of wavefunction collapse. It
| took me a very long time to come to terms with the idea
| of a non-deterministic universe.
| mensetmanusman wrote:
| It's interesting that many things are deterministic to
| human-relevant time/length scales. If the small stuff is
| non-deterministic, it's interesting that large ensembles
| of them are quite deterministic.
|
| It's maddening :)
| sva_ wrote:
| That's peculiar. Most people probably struggle more with
| the idea of a deterministic universe, as it'd leave no
| room for free will, which would make everything kind of
| meaningless.
|
| I'm also more in the camp of "quantum effects making the
| universe non-determinstic." It's a nicer way to live.
| dekhn wrote:
| I've evolved over the years from "determinism implies no
| free will" to roughly being a compatibilist
| (https://en.wikipedia.org/wiki/Compatibilism, see also
| Daniel Dennett). I don't particularly spend much time
| thinking that (for example) a nondeterministic universe
| is required for free will. I do think from an objective
| sense the universe is "meaningless", but that as humans
| with agency we can make our own meaning.
|
| However, most importantly, we simply have no experimental
| data around any of this for me to decide. Instead I enjoy
| my subjective life with apparent free will, regardless of
| how the machinery of the actual implementation works.
| Taylor_OD wrote:
| It's a bit naive... But the best argument for me that we are
| living in a simulation is that we went from Pong to pretty
| good VR (good enough that if you have a beer or two before
| using you can forget its VR for some period of time) in 50
| years. In another 50 years it seems fair to assume that we
| will be able to create VR that fully immersive and impossible
| to distinguish from real life.
|
| Even with no other arguments about the benefits of WHY one
| would want to live in a fully simulated world... It seems
| probable to me that we are based on the idea that it could be
| possible.
| iamstupidsimple wrote:
| > In another 50 years it seems fair to assume that we will
| be able to create VR that fully immersive and impossible to
| distinguish from real life.
|
| Technology growth is always non-linear. it's also fair to
| assume we could stagnate for 50 years also.
| kingofclams wrote:
| https://qntm.org/responsibility
| joseluis wrote:
| we don't even need to be able to calculate everything, we
| just need to fool you! The Truman's show meets the Matrix.
| amself wrote:
| I went through the same phase at 12. I am nearing 18 now, and
| I am very thankful for nondeterminism.
| tsol wrote:
| Looking at it from that view, we're just as likely to be a
| simulation as we are to have been created by God. I mean I'm
| a theist, but I don't see many huge differences except the
| cultural aspect where the theism/atheism debate is something
| most people have an emotional connection to.
| KarlKemp wrote:
| A God, not being out for her own amusement, will likely
| create only one universe.
|
| A player with a simulator will create dozens.
| tsol wrote:
| >A God, not being out for her own amusement, will likely
| create only one universe.
|
| Why would that be? I see no reason why God might not
| create parallel universes
| coolspot wrote:
| Electrical bill and GPU shortages in God's reality could
| be a reason.
| reasonabl_human wrote:
| If you want to solve that nagging thought, pick up Griffith's
| intro to quantum mechanics textbook. Goes through the
| philosophical implications of qm alongside learning the
| physics. The world as we know it is non-deterministic thanks
| to wave functions and their random collapsing!
| benlivengood wrote:
| The thought that sticks in my mind is mathematical realism;
| if we can prove the mathematical existence of the outcome of
| a simulation (nothing harder than inductively showing that
| the state of a simulation is well-defined at state S for the
| first and all successive S) then what's the difference
| between things in the simulation actually existing v.s.
| possibly existing? All of the relationships that matter
| between states of the simulation are already proven to exist
| if we looked at (calculated) them, so what necessary property
| can we imagine our Universe having that the possible
| simulation does not?
| visarga wrote:
| > so what necessary property can we imagine our Universe
| having that the possible simulation does not?
|
| It lacks the magical spark, the qualia, the spirit, the
| transcendent. Or what people like to imagine makes our own
| reality special. Our own reality cannot be understood
| because it's such a hard problem, and it "feels like
| something" (maybe like a bat?), while a simulation is just
| math on CPUs. Consciousness is a hard problem because it
| transcends physical sciences, it's so great that it can
| exist even outside the realm of verification. /s
|
| Hope you forgive the rant, it's just amazing how much
| philosophy can come from the desire to fly above the
| mechanics of life. But what they missed is that the reality
| of what happens inside of us is even more amazing than
| their imaginary hard problem and special subjective
| experience. The should look at the whole system, the whole
| game, not just the neural correlates. What does it take to
| exist like us?
| VikingCoder wrote:
| A simulated hurricane doesn't kill anyone.
|
| But it may be possible that there's no such thing as
| "simulating" intelligence. If you do certain calculations,
| that is "intelligent." Same for consciousness, etc.
| wrinkl3 wrote:
| A simulated hurricane would kill simulated people.
| tsol wrote:
| Think of simulated children! Oh the simulated pain..
| disease wrote:
| "We live inside a dream."
| agentultra wrote:
| Specifically, I'm referring to _Autoverse_ , the artificial
| simulation of a single bacterium down to the atomic level.
|
| It was such a fascinating idea that I found myself more than
| once trying to mimic the atomic part at a much smaller scale
| over the years.
| webmaven wrote:
| _> Permutation City, here we come._
|
| You might enjoy the show Devs:
|
| https://en.m.wikipedia.org/wiki/Devs
|
| Fair non-spoilery warning, there is quite a bit of creepy
| existential angst.
| stronglikedan wrote:
| > there is quite a bit of creepy existential angst
|
| seems to be a trend across all genres nowadays
| webmaven wrote:
| Sure. Though most of it isn't _literally_ existential.
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