Jump to content

Talk:Molecular dynamics

Page contents not supported in other languages.
From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by Opabinia regalis (talk | contribs) at 05:47, 7 September 2015 (→Paragraph to remove: good job autocorrect!). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.


Examples of applications

This section seems like trivia for now (perhaps it could be useful if it gave a comprehensive listing of types of simulations that people run, but until then I think that the page would be better without it).

Additionally, because computers continue to get faster, listings of "very long simulations" get stale rather quickly. The simulations cited in the section following the text "The following two biophysical examples are not run-of-the-mill MD simulations" are now no longer the longest simulations or the biggest systems simulated to date. In fact, simulation studies totalling 0.5 ms are no longer particularly rare (note that this "0.5 ms simulation" noted in the article is not a single continuous simulation but the aggregated simulation time of many shorter simulations).

Finally, there is a danger that a section like this is simply an advertisement for a biased selection of work. — Preceding unsigned comment added by 108.161.122.218 (talk) 19:11, 23 September 2012 (UTC)[reply]

Merge with Molecular dynamics

The whole article is highly redundant--92.205.19.67 (talk) 10:35, 12 February 2014 (UTC) — Preceding unsigned comment added by 92.192.57.120 (talk) [reply]

  • It is an opportunity to improve the article, but do not to merge. These things are considerably different. — Preceding unsigned comment added by P99am (talk • contribs)
Yep, Second Quantization (talk) 09:28, 20 February 2014 (UTC)[reply]

The flow diagram below infobox is missing velocity update

It is crucially missing v=v+a*dt. Am I right? Oceangai (talk) 23:45, 27 February 2014 (UTC)[reply]

I think you are correct. Sizeofint (talk) 03:33, 21 May 2015 (UTC)[reply]

Yes, of course it was missing it, it was a simplified one (made by me). But instead of just removing it, please make a better one then and add it there. Just removing other people stuff without providing an improved version is not very constructive. — Preceding unsigned comment added by 128.214.7.97 (talk) 06:40, 11 June 2015 (UTC)[reply]

I now added a much more detailed MD algorithm schematic -- of course this is not exactly correct either, it is impossible to make an exactly correct one in a schematic. If anybody is not happy with this, don:'t remove it, but replace it with a better one. Knordlun (talk) 09:32, 7 July 2015 (UTC)[reply]

Looks great! Thanks! Sizeofint (talk) 15:39, 7 July 2015 (UTC)[reply]

Mistaken summation?

Unless I'm misunderstanding something... in the section 'Pair potentials versus many-body potentials', in the second equation (for U sub i,j) of that section, the first term should not have a summation, right?

Sincerely, DrTLesterThomas (talk) 18:43, 19 February 2015 (UTC)[reply]

Should any of the terms have summations? If this is the potential between a pair of particles why sum over all particles? Sizeofint (talk) 03:50, 21 May 2015 (UTC)[reply]

Paragraph to remove

I propose to delete the paragraph beginning with the words "Some results of simulations ..." This section contains some amateur discussion of protein folding problem. In spite of the serious references the text is misleading. Article does not lose anything because this section is not about MD itself but about the specific problem. P99am (talk) 09:35, 21 June 2015 (UTC)[reply]

Agreed Sizeofint (talk) 15:43, 21 June 2015 (UTC)[reply]
This is a complicated issue to discuss. Hence just a few points.
  1. I agree that text should be probably rearranged to clarify that it was about MD in general, rather than about protein folding (protein folding is simply an example that clarifies what the general problems are);
  2. Nothing in the underlying force fields which are currently used has fundamentally changed during this time to my knowledge, so all arguments and sources are still valid.
  3. If you or anyone else want to bring newer publications on the subject of MD applicability (and I know that a lot has been published), they are more than welcome. For example, someone might think that polarizable force fields helped to resolve any problems described in the "limitations" section. If so, one should simply describe: (a) what the problems are/were, and (b) how exactly they have been resolved - per sources. I can not do it because to my knowledge these problems have not been resolved. If they were resolved, we would had precise 3D models of all proteins from numerous genomes generated by energy minimization and MD. But we only have very poor quality models generated at the Protein Model Portal by very old and primitive homology modeling because it works much better than "ab initio" MD. My very best wishes (talk) 01:54, 4 September 2015 (UTC)[reply]
  4. P.S. If Michael Levitt changed his opinion about MD, this should be noted. My very best wishes (talk) 02:14, 4 September 2015 (UTC)[reply]
While there haven't been any fundamental changes in the basic model, there have been significant advances in the quality of the force field parameters - as judged by e.g. comparison to NMR measurements - and in the compute resources available, as well as a correspondingly deeper appreciation of protein conformational variability on the experimental side of things. None of that stuff is a game-changer on its own but collectively the relative weights of different problems have changed quite a bit with respect to application to proteins.
I don't know if Levitt himself has changed his opinion about MD, but the quote highlighted in the article really does sound like old business. Overall interest in CASP has declined, Rosetta is everywhere, and model refinement isn't really a common use case, current or anticipated, for MD. The model portal and similar 'model the proteome' style projects have always been mostly grant bait, and polarizability is vaporware.
I started to rewrite some of this but it's too much like doing work after work ;) At least the applications sentence should really be refactored; putting docking first has to be some kind of clever troll. Docking people outside of Schrödinger can't seem to stand MD. Opabinia regalis (talk) 06:44, 4 September 2015 (UTC)[reply]
That's fine. But we need a "criticism" section written in a language people can understand. OK, let's say it in a different way. People who use this method tend to think that they are seeing actual/real movements of atoms. Yes, in a way they do - in a very crude approximation, and on a limited time scale. However, method fail during simulations of complex processes, such as protein folding. That has been openly admitted by a scientist who received Nobel prize for developing and applying this method to proteins. This is happening because the underlying "potential energy" functions do not directly account for a number of fundamentally important factors, such as the environment-dependence of interatomic interactions, hydrophobic interactions and conformational entropy. That's why "docking people" usually do not use MD (actually, some of them do) - exactly as you tell. That's why people are developing alternative energy functions, even such as statistical potential. My very best wishes (talk) 13:16, 4 September 2015 (UTC)[reply]
I suppose I'm circuitously getting back around to your point 1, that a discussion of limitations should distinguish between the general limitations that arise due to the approximations made in modeling the underlying physics, and the issues that apply to specific use cases. Poor-quality force field parameters is an issue with a foot on either side of the fence, and if you believe any of the DE Shaw papers from a couple of years ago (e.g. PMID 22513870), is the most significant obstacle to both protein folding and model refinement (at least, if you have vast amounts of computing resources to throw at the issue). Opabinia regalis (talk) 04:31, 5 September 2015 (UTC)[reply]
Yes, I think this paper by Shaw is worth mentioning, even though he did this in "post-diction" (not prediction/CASP) regime. The CASPs are indeed important as the only believable way to assess the computational methods, most of which are not MD. The problems/limitations are very general but they become more apparent when one deals with global energy minimization of a complex system. In this case one should be looking for the global minimum of Gibbs free energy difference (relative to the coil in aqueous solution for proteins). Some people who do MD simulations are claiming to achieve just that, ironically with coarse-grained models. Can they do something real and better than using other methods? Only CASP can answer, but for someone who understands the physics the answer is "no". My very best wishes (talk) 12:51, 5 September 2015 (UTC)[reply]
Yes, I would suggest this review: PMID 24463371 from the Shaw group also, and a benchmark of modern force fields against NMR parameters, e.g. PMID 22754404 from Pande.
From the view of a physicist, yes, the deficiencies are general and irresolvable without modifying the model. From the view of a protein biochemist, the deficiencies are relevant only to the extent that they affect the results, which for most uses are not ab initio predictions of folded globular structures. (Arguably most usage of MD by experimentalists is as a confirmation bias engine, but that's OR... ;) Opabinia regalis (talk) 05:46, 7 September 2015 (UTC)[reply]
Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Talk:Molecular_dynamics&oldid=679854137"