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madez commented on Anton (Computer)   en.wikipedia.org/wiki/Ant... · Posted by u/bane
tchitra · 5 years ago
That's a good question and there are a number of ways to try to tackle this. One of the main reasons you cannot do QM simulations directly is that the high quality methods can cost Omega(n^6/eps) to get eps. relative accuracy (you can do better with DFT, but then you're making your life hard in other way). At a high-level (and I mean, 50,000 ft. level), here are the simplest way:

1) Do quantum mechanics simulations of interactions of a small number of atoms — two amino acids, two ethanol molecules. Then fit a classical function to the surface E[energy(radius between molecules, angles)], where this expectation operator is the quantum one (over some separable Hilbert space). Now use the approximation for E[energy(r, a)] to act as your classical potential. - Upshot: You use quantum mechanics to decide a classical potential for you (e.g. you chose the classical potential that factors into pairs such that each pair energy is 'closest' in the Hilbert space metric to the quantum surface) - Downside: You're doing this for small N — this ignores triplet and higher interactions. You're missing the variance and other higher moments (which is usually fine for biology, FWIW, but not for, say, the Aharanov-Bohm effect).

2) Path Integral methods: This involves running classical simulation for T timesteps, then sampling the 'quantum-sensitive pieces' (e.g. highly polar parts) in a stochastic way. This works because Wick rotation lets you go from Hamiltonian evolution operator e^{i L}, for a Lagrangian density L, to e^{-L} [0]. You can sample the last density via stochastic methods to add a SDE-like correction to your classical simulation. This way, you simulate the classical trajectory and have the quantum portions 'randomly' kick that trajectory based on a real Lagrangian.

3) DFT-augmented potentials: A little more annoying to describe, but think of this as a combination of the first two methods. A lot of the "Neural Network for MD" stuff falls closer in this category [1]

[0] Yes, assume L is absolutely continuous with regards to whatever metric-measure space and base measure you're defined over :) Physics is more flexible than math, so you can make such assumption and avoid thinking about nuclear spaces and atomic measures until really needed

[1] https://arxiv.org/abs/2002.02948

madez · 5 years ago
> Upshot: You use quantum mechanics to decide a classical potential for you (e.g. you chose the classical potential that factors into pairs such that each pair energy is 'closest' in the Hilbert space metric to the quantum rest) - Downside: You're missing the variance.

Couldn't the quantum mechanical state become multimodal such that the classical approximation picks a state that is far away from the physical reality?

And, couldn't this multimodality excaberate during the actual physical process and possibly arrive at a number of probable outcomes which are never predicted by the simulation? Is there more than hope that that doesn't happen?

madez commented on Anton (Computer)   en.wikipedia.org/wiki/Ant... · Posted by u/bane
tchitra · 5 years ago
[Disclaimer: I used to work at D. E. Shaw Research from 2011-2016]

The early Anton 1 numbers of 17us/day on 100K atoms were huge leap forward then. At that time, GPU-based simulations (e.g. GROMACS/Desmond on GPU) were doing single digit ns/day. Remember, even for 'fast-folding' proteins, the relaxation time is on the order of us and you need 100s of samples before you can converge statistical properties, like folding rates [0]. Anton 2 got a 50-100x speed-up [1] which made it much easier to look at druggable pathways. Anton was also used for studying other condensed matter systems, such as supercooled liquids [2].

Your question of why is this so slow or small is prescient. On the reasons that we have to integrate the dynamical equations (e.g. Newtonian or Hamiltonian mechanics) at small, femtosecond timesteps (1 fs = 1e-15s) is because the vibrational frequencies of bonds are on the order of picoseconds (1 ps = 1e-12s). Given that you also have to compute Omega(n^2) pairwise interactions between n particles, you end up having a large runtime to get to ns and us while respecting bond frequencies. The hard part, for atomistic/all-atom simulation is that n is on the order of 1e5-1e6 for a single protein with 100s of water molecules. The water molecules are extremely important to simulate exactly since you need to get polar phenomena, such as hydrogen bonding, correct to get folded structure and druggable sites correct to angstrom precision (1e-10 meters). If you don't do atomistic simulations (e.g. n is much smaller and you ignore complex physical interactions, including semi-quantum interactions), you have a much harder time matching precision experiments.

[0] https://science.sciencemag.org/content/334/6055/517

[1] https://ieeexplore.ieee.org/abstract/document/7012191/ [the variance comes from the fact that different physics models and densities cause very different run times -> evaluating 1/r^6 vs. 1/r^12 in fixed precision is very different w.r.t communication complexity and Ewald times and FFTs and ...]

[2] https://pubs.acs.org/doi/abs/10.1021/jp402102w

madez · 5 years ago
This explanation is interesting. Thanks for sharing it. While reading it, I got the impression that the simulation is not fully quantum mechanical, but rather classical with select quantum mechanical effects.

Which parts of quantum mechanics are idealised away and how do we know that not including them won't significantly reduce the quality of the result?

Are you possibly using stochastical noise in the simulations and repeat them multiple times, in the hope that whatever disturbance caused by the idealisation of the model is covered by the noise?

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madez commented on Criminal investigation at Austrian ski resort where hundreds were infected   telegraph.co.uk/news/2020... · Posted by u/ajaviaad
KarlKemp · 5 years ago
You’re suggesting copyright is obsolete because technical means of protecting content are so easy to circumvent.

That’s absurd, considering laws protecting rights that are easily protected by, for example, physical means are entirely unnecessary.

The only reason we have laws against burglary is to allow us the benefits of not living in a personal fortress. To turn this around and deny anyone going out in public without a personal protection detail the benefit of laws against being robbed or raped is indistinguishable from just scrapping all criminal law.

The other, more common and less interesting (but equally wrong), assumption you’re making is that there is some secret business model that thousands of publications and journalists have somehow missed to see. Or, alternatively, the strange situation of gleefully enjoying the decline of journalism, coming up with all sorts of accusations to deny that their work has any value for you or society, while simultaneously spending 8+ hours these days reading their work.

madez · 5 years ago
I'm saying that copyright is unjust. It violates fundamental individual freedoms of people like freedom of expression to achieve goals that do not justify that mean, and is therefore illegitimate.

The comparison to laws that protect people is invalid because copyright does not protect people. It grants governmentally enforced monopolies. Copyright has a legitimate goal. There is a value in certain activities for society and copyright is a governments intervention to increase that activity.

There are other things that are considered so important that the government takes action to provide them, like for example social security, health services and infrastructure. That is realized by taxation. I'm suggesting that the state should use taxation to ensure the activity of those who rely now on copyright so the restrictions of individual fundamental freedoms is gone.

Note that copyright has become even more restrictive with time. There are situations where people are forbidden from singing a song on a birthday party in public. This is an example of where the unjust restriction of individual freedoms becomes apparent.

And I'm saying that this injustice in some situations is so grave, that we should show civil disobedience and try to break and mock copyright when possible as a form of protest.

madez commented on Criminal investigation at Austrian ski resort where hundreds were infected   telegraph.co.uk/news/2020... · Posted by u/ajaviaad
mathieuh · 5 years ago
Prefix the URL with outline.com/

Mods please let me know if this not allowed

madez · 5 years ago
Copyright does not deserve voluntary submission anyways. It is an unjust and ever stricter becoming legal framework to give life support to an industry that is unwilling to adjust to new technological realities.
madez commented on Retroshare: Secure Communication for Everyone   retroshare.cc/... · Posted by u/spking
madez · 5 years ago
RetroShare was removed from Debian in the past. Anybody any clues why?
madez commented on Popcorn Time 4.0   github.com/popcorn-offici... · Posted by u/ncdlek
1_player · 5 years ago
Say what you will about stealing, illegality, unsavouriness.

If the film industry would collectively take their head out of their arses and provide such a simple interface and wide catalogue to the masses, they would make hundreds of billions.

I would literally pay $50 a month for an official and legal version of this.

The end users don't really care that it is not possible because "legal reasons". This app proves otherwise and I wholeheartedly approve of their mission.

EDIT: if I would pay $50 a month, why am I not buying/renting movies on iTunes or Amazon for the same amount? For the same reason Spotify or Apple Music are making a killing. Give me a flat rate and let me watch _everything_, it's hard to decide if that new movie just out is worth spending $15 on. Might be crap.

madez · 5 years ago
It is not stealing. It may be illegal, but it isn't stealing nor robbery. You may be violating the copyright law, but nobody is taken away any object and there is no threat of violence. When people get access to copyrighted works, then at first, it is good for people. Only then the idea is that the creators can't make a living by producing those works. We can solve that differently, without using copyright. Copyright is a weirdly anti-market and authoritarian concept where the government artificially makes something scarce by punishing supply. In any case, distributing stuff is not stealing. /rant
madez commented on Firm wielding Theranos patents asks judge to block coronavirus test   arstechnica.com/tech-poli... · Posted by u/ohjeez
hn_throwaway_99 · 5 years ago
One thing that I hope will come out of this coronavirus event, even if just for a short while, is that people no longer at large accept that this anti-social behavior is just "doing business".

And I realize the article was updated to give a "royalty free license", which is complete and total bullshit because BioFire shouldn't need a license for Theranos' bullshit patents that never worked anyway.

We need to start naming and shaming for this kind of trolling, anti-social behavior. And not just the company name, I'm talking about the principals and lawyers who filed this, who are nothing but a net-negative to society.

madez · 5 years ago
"I'm just doing my job!"

The deflection of personal responsibility for damaging behaviour as part of a job is a cultural problem.

madez commented on Germany and US wrestle over coronavirus vaccine   dw.com/en/germany-and-us-... · Posted by u/misotaur
theferalrobot · 5 years ago
Which is reporting on the initial article which again just states that Germany said the US was trying to invest in the company, not that they were looking for an exclusive arrangement. Show me where Germany confirmed that the US was looking for an exclusive arrangement, we have multiple people saying this was not the case.
madez · 5 years ago
That's not what is said in the article of politico. Here is what is reported:

First, The allegation:

According to the article, Trump was trying to get the Tübingen-based CureVac company — which also has sites in Frankfurt and Boston — to move its research wing to the United States and develop the vaccine "for the U.S. only."

Then, the government acknowledgement:

A spokesperson for Germany's Health Ministry quoted in the article appeared to acknowledge the U.S. approach and said that Berlin was "very interested in ensuring that vaccines and active substances against the new coronavirus are also developed in Germany and Europe."

Who says this is incorrect? The alleged party? Because the company did not deny that it was approached by the US American government to sell exclusive access. It just denied that it will be bought, which is a different thing. Regarding the exclusivity it has declared that it will ensure that the vaccine will be available to the world, without neither confirming nor denying the allegation. The fact that they clarify that (source: https://www.curevac.com/news/curevac-focuses-on-the-developm...) the fact that the German government acted at all (multiple reports of that exist), and the fact that the CEO of the company was fired (the company has a press release about it) after meeting Trump are further evidence that indeed an exclusive deal was sought.

u/madez

KarmaCake day3080November 19, 2014View Original