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Is this simulation on the atomic level with full all interatomic physics processes simulation or there were made some simplifications? All interatomic interact

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.

Frost1x 5y ago
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/UsersGuide.pdf http://faculty.scs.illinois.edu/schulten/lm/download/lm23/Us...
- dahart 5y ago
  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 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.”
- vasili111 5y ago
  For anyone who is wondering what QED is: Quantum electrodynamics (QED) https://en.wikipedia.org/wiki/Quantum_electrodynamics https://en.wikipedia.org/wiki/Quantum_electrodynamics
  - kingcharles 5y ago
    Ah, should have realized when Quad Erat Demonstradum made no sense...!
    - tobmlt 5y ago
      I've always imagined Feynman making a QED, QED joke sometime in the late 1940's for this very reason. Like he could end his Shelter Island Conference talk with the joke and then look up from the blackboard... to a bunch of confused and deeply furrowed brows, lol.
deleted 5y ago
[deleted]
CorrectHorseBat 5y ago
Of course not, we can't even simulate how one protein folds.
- Cthulhu_ 5y ago
  What does https://foldingathome.org/ https://foldingathome.org/ do then? That's been going on for nearly two decades.
  - echelon 5y ago
    Simulating very expensive to compute protein dynamics. These aren't guaranteed solutions, but it's still useful information.
    - vasili111 5y ago
      So, even one protein cannot be simulated as in real world?
      - beecafe 5y ago
        One single iron atom's electrons - 26 of them - contain more degrees of freedom than atoms in the solar system.
      - qboltz 5y ago
        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 5y ago
        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
gfd 5y ago
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.
- dekhn 5y ago
  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 5y ago
    All of our current theories are set in continuous spacetime. At the present, there's no reason to assume anything else.
    - dekhn 5y ago
      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 5y ago
      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.
alpineidyll3 5y ago
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 5y ago
>"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 https://en.wikipedia.org/wiki/Full_configuration_interaction
- sseagull 5y ago
  It’s worse than exponential, it’s factorial :)
- unemphysbro 5y ago
  verlet list is the standard algo used to reduce the complexity in the number of interatomic calculations https://en.wikipedia.org/wiki/Verlet_list https://en.wikipedia.org/wiki/Verlet_list
  - dekhn 5y ago
    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 5y ago
      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 5y ago
        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 https://en.wikipedia.org/wiki/Ewald_summation), once you wrap your head around it!
marcosdumay 5y ago
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 5y ago
  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.
  - chermi 5y ago
    Excuse formatting, one phone. Was gonna put more refs... But phone. Yes, this is not the standard "force field" pairwise stuff you're used to when you heard "simulation" of biomolecular systems. I don't know if it's quite disingenuous, just not what we expect based on what the vast, vast majority of the field does! It does represent that many atoms. We shouldn't include atoms for the sake of having them, right? It should depend on what questions we're asking of the system. I like seeing other (simulation or analytic) methods get attention. Lattice methods --(HP models[0], for hydrophobicity[1], lattice-boltzmann even. field theoretic (see polymer physics, melts, old theory[2], new theory, and even newer simulation[3]). Even the simplest shit like springs[4]! [0] https://scholar.google.com/citations?view_op=view_citation&hl=en&user=t3u4Y3EAAAAJ&citation_for_view=t3u4Y3EAAAAJ:d1gkVwhDpl0C https://scholar.google.com/citations?view_op=view_citation&h... [1] https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.112.020603 https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.11... [2]https://www.google.com/books/edition/Renormalization_Group_Theory_of_Macromol/Hgt2QgAACAAJ?hl=en https://www.google.com/books/edition/Renormalization_Group_T... [3]The Equilibrium Theory of Inhomogeneous Polymers (International Series of Monographs on Physics) https://www.amazon.com/dp/0199673799/ref=cm_sw_r_apan_glt_i_CVCSPQ4Z4C8Y40Q674RC https://www.amazon.com/dp/0199673799/ref=cm_sw_r_apan_glt_i_... (numerical scft) [4] https://en.m.wikipedia.org/wiki/Gaussian_network_model https://en.m.wikipedia.org/wiki/Gaussian_network_model

Frost1x 5y ago

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/UsersGuide.pdf http://faculty.scs.illinois.edu/schulten/lm/download/lm23/Us...

dahart 5y ago
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 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.”
vasili111 5y ago
For anyone who is wondering what QED is: Quantum electrodynamics (QED) https://en.wikipedia.org/wiki/Quantum_electrodynamics https://en.wikipedia.org/wiki/Quantum_electrodynamics
- kingcharles 5y ago
  Ah, should have realized when Quad Erat Demonstradum made no sense...!
  - tobmlt 5y ago
    I've always imagined Feynman making a QED, QED joke sometime in the late 1940's for this very reason. Like he could end his Shelter Island Conference talk with the joke and then look up from the blackboard... to a bunch of confused and deeply furrowed brows, lol.

deleted 5y ago

[deleted]

CorrectHorseBat 5y ago

Of course not, we can't even simulate how one protein folds.

Cthulhu_ 5y ago
What does https://foldingathome.org/ https://foldingathome.org/ do then? That's been going on for nearly two decades.
- echelon 5y ago
  Simulating very expensive to compute protein dynamics. These aren't guaranteed solutions, but it's still useful information.
  - vasili111 5y ago
    So, even one protein cannot be simulated as in real world?
    - beecafe 5y ago
      One single iron atom's electrons - 26 of them - contain more degrees of freedom than atoms in the solar system.
    - qboltz 5y ago
      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 5y ago
        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

gfd 5y ago

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.

dekhn 5y ago
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 5y ago
  All of our current theories are set in continuous spacetime. At the present, there's no reason to assume anything else.
  - dekhn 5y ago
    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 5y ago
    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.

alpineidyll3 5y ago

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 5y ago

>"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 https://en.wikipedia.org/wiki/Full_configuration_interaction

sseagull 5y ago
It’s worse than exponential, it’s factorial :)
unemphysbro 5y ago
verlet list is the standard algo used to reduce the complexity in the number of interatomic calculations https://en.wikipedia.org/wiki/Verlet_list https://en.wikipedia.org/wiki/Verlet_list
- dekhn 5y ago
  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 5y ago
    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 5y ago
      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 https://en.wikipedia.org/wiki/Ewald_summation), once you wrap your head around it!

marcosdumay 5y ago

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 5y ago
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.
- chermi 5y ago
  Excuse formatting, one phone. Was gonna put more refs... But phone. Yes, this is not the standard "force field" pairwise stuff you're used to when you heard "simulation" of biomolecular systems. I don't know if it's quite disingenuous, just not what we expect based on what the vast, vast majority of the field does! It does represent that many atoms. We shouldn't include atoms for the sake of having them, right? It should depend on what questions we're asking of the system. I like seeing other (simulation or analytic) methods get attention. Lattice methods --(HP models[0], for hydrophobicity[1], lattice-boltzmann even. field theoretic (see polymer physics, melts, old theory[2], new theory, and even newer simulation[3]). Even the simplest shit like springs[4]! [0] https://scholar.google.com/citations?view_op=view_citation&hl=en&user=t3u4Y3EAAAAJ&citation_for_view=t3u4Y3EAAAAJ:d1gkVwhDpl0C https://scholar.google.com/citations?view_op=view_citation&h... [1] https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.112.020603 https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.11... [2]https://www.google.com/books/edition/Renormalization_Group_Theory_of_Macromol/Hgt2QgAACAAJ?hl=en https://www.google.com/books/edition/Renormalization_Group_T... [3]The Equilibrium Theory of Inhomogeneous Polymers (International Series of Monographs on Physics) https://www.amazon.com/dp/0199673799/ref=cm_sw_r_apan_glt_i_CVCSPQ4Z4C8Y40Q674RC https://www.amazon.com/dp/0199673799/ref=cm_sw_r_apan_glt_i_... (numerical scft) [4] https://en.m.wikipedia.org/wiki/Gaussian_network_model https://en.m.wikipedia.org/wiki/Gaussian_network_model