Talk:Protein structure prediction

message: In the third paragraph, should comparative structure prediction be linked to comparative protein modeling? 98.192.58.208 21:23, 17 October 2007 (UTC)
thread_title: Comparative structure prediction 

message: I have a couple of suggested amendments to the text.
: Davjon, be bold and make the changes! Stewart Adcock 19:05, 21 Mar 2004 (UTC)
replies: text: Yes, the article is not very clear on this point. Stewart Adcock 19:05, 21 Mar 2004 (UTC)
thread_title:  chaperonins 

message: Having said that, an additional complication is that some proteins are only able to fold into their biologically useful conformation under particular conditions (e.g. high pH or low temperature) or in the presence of other molecules (e.g. metals) or even other protein chains (in the formation of certain protein complexes). User:Davjon 08:35, 20 March 2004 
: You are, of course, correct again.  But the problem is on deciding how much information you want to put in the article while still keeping it simple and understandable.  Most readers will have very little background knowledge about proteins. Stewart Adcock 19:05, 21 Mar 2004 (UTC)
replies: text:  I have modified the article to reflect the lack of evidence that primary sequence does not determine protein folding. I noted that chaperones and glycosylation can be important in protein folding. --Antelan 20:52, 4 October 2006 (UTC)
thread_title:  conditional conformation 

message: I reverted two recent changes.  Here's why:
:1. restored link to "X-ray crystallography" over "crystallography" because very few protein structures are solved by electron/neutron diffraction (not surprising since they destroy the sample).
:2. first sentence.  "Computational biology" is something very different to "Computational molecular biology".  The most appropriate article on wikipedia seems to be bioinformatics so I've pointed the link at that.
Stewart Adcock 00:04, 2 Feb 2004 (UTC)
replies: text: I've added theoretical chemistry because ab initio calculations belong to that field. --Zivilverteidigung
Back in the pre-genome pre-proteomics era, quite a few structures were determined by neutrons. Electrons are essential to do 2D crystallography of membrane proteins, which is all you can do with most of them. The sentence as you have it now is reasonable with "typically" and X-ray crystallography, but I consider crystallography a much better article. Really I think the two should be merged.168... 00:14, 2 Feb 2004 (UTC)
thread_title:  crystallography terms 

message: Hi everyone, I was wondering whether it is appropriate to mention that another method to determine a partial protein structure are studies investigating ligand binding sites; in particular, the use of ligand analogues to determine the binding site's spacial features. I know it's only a partial structure, but should it be mentioned here? Volantares 12:25, 7 December 2006 (UTC)
replies: text: That would be of interest if you have any particular references on the subject, often information gathered from the literature is used as hint by the CASP competitors but in an empirical way. If there is a methodology to retrieve structural information from ligand binding that would be worth mentioning, if it's just personal research no. Blastwizard 18:45, 7 December 2006 (UTC)
thread_title: Ligand binding 

message: The software for structure prediction could use a major overhaul, or should just link to the dedicated software page. —The preceding unsigned comment was added by Mndoci (talk • contribs) 20:55, 5 February 2007 (UTC)
thread_title:  The software section needs a major revamp 

message: Within the Software section, reference might be made to a new prediction engine called LOMETS from Wu and Zhang at U of Kansas.  The announcement article is 
Wu S, Zhang Y.  LOMETS: a local meta-threading-server for protein structure prediction.  Nucleic Acids Res. 2007;35(10):3375-82. Epub 2007 May 3.
LOMETS is a tuned consensus of 9 engines, all supported in a server cluster by the authors.
152.2.146.67 22:19, 17 June 2007 (UTC)
thread_title:  adding a new reference to "protein structure prediction" 

message: "The practical role of protein structure prediction is now more important than ever." The phrase sounds like an advertisement. Perhaps something more concrete... "Protein structure prediction bridges the increasing divide between the faster modern sequence gathering technologies and the slower protein analysis [...etc]"JeramieHicks (talk) 23:12, 21 November 2008 (UTC)
thread_title:  Now More Important Than Ever 

message: I am not a scientist, so pardon if this is a stupid question. How does homochirality factor into modeling algorithms? Since every molecule is capable of being arranged into an identical mirror image, but the mirror image is often inactive or toxic, then it would appear that half the search space can be thrown away and not computed. DMahalko (talk) 20:59, 11 May 2009 (UTC)
replies: text: Homology modelling algoritms already ignore the D form of the residues, since they only occur in extremely rare cases in bacteria so nothing new there Blastwizard (talk) 09:19, 24 June 2009 (UTC)
thread_title:  How does homochirality factor into modeling? 

message: CASP is not about automatic structure prediction servers, this is a confusion with CAFASP. In CASP, human prediction are also assessed although human prediction normally involves manually fiddling with server predictions.
Also why reducing this section to the CASP experiment? Blastwizard (talk) 09:26, 24 June 2009 (UTC)
thread_title:  Automatic structure prediction servers 

message: I would like to know whether the commonly used computer programs always give a free energy for the native structure (as determined by NMR  or X-rays) less than or equal to that for the best solutions that the programs find. (If someone answers, drop me a note please.) Eric Kvaalen (talk) 14:55, 13 August 2010 (UTC)
replies: text: Of course not. A typical program would produce something like minus several thousand kcal/mol calculated with CHARMM or another force field. This  suppose to be enthalpy in vacuum/vapor, which is totally irrelevant to protein folding, ligand binding or anything of biological significance (but this number is not even this enthalpy because force fields neglect the environment-dependence of vDW and other forces).Biophys (talk) 18:08, 13 August 2010 (UTC)
replies: text: But as the article says, "The protein structure prediction remains an extremely difficult and unresolved undertaking. The two main problems are calculation of protein free energy and finding the global minimum of this energy. A protein structure prediction method must explore the space of possible protein structures which is astronomically large." I have read that Rosetta for instance calculates free energy. My question is not whether the energy calculation is really good, my question is whether if you put the true structure in, the program will agree that its free energy is lower than (or equal to) the free energy of what it came up with. In other words, do the programs fail to find the true configuration because they don't manage to find the true minimum (according to their energy functions), or because their energy functions are slightly wrong, so even if they find the true minimum according to those functions, it doesn't correspond to the conformation that minimizes the true free energy. Eric Kvaalen (talk) 12:06, 14 August 2010 (UTC)
replies: text: Rosetta combines force fields in vacuum (in modified form) with empirical terms that describe free energy of solvation and conformational entropy. The key question: can it reproduce experimental deltaG differences  between unfolded state and folded protein structure? Such values are measured for hundreds proteins and rather small (only several kcal/mol). There are empirical free energy functions (not MM force fields) that claim to reproduce delta deltaG values for protein mutants and deltaG of ligand binding with a reasonable precision. Are these functions good enough to distinguish the native and misfolded structures (that sometimes differ only by 3-4 kcal/mol according to experimental studies) is a hard question. I think the answer is "no" in general, but "yes" for certain special cases, but this is a matter of ongoing "original research".Biophys (talk) 19:32, 14 August 2010 (UTC)
replies: text: Thanks for the reply. 3-4 kcal/mol is actually a lot, since RT is only 0.6 kcal/mol. I hope you'll come back with your results. You can put original research here on the discussion page. Eric Kvaalen (talk) 10:26, 17 August 2010 (UTC)
replies: text: Posting WP:OR here would be against the policies. Obviously, this should be larger than RT. Otherwise, the system would be unstable. No, 3-4 kcal/mol is actually nothing compare to 3-4 thousands kcal/mol produced by CHARMM for a typical protein. The CHARMM energy of an unfolded proteins would also be large. So, let's subtract one from another and do not forget about conformational entropy that could be ~ 1-2.5 kcal/mol per residue at 300K? Be serious. Assuming an error of ~10% in 6-12 potential functions, it would be statistically impossible to calculate the small difference with the required precision (article by Galaktionov in Russian "Biophysics"). The real problem however that such functions have been developed to calculate irrelevant energy (yes, that's an energy, but not the energy one needs - this is something rather common in physics).Biophys (talk) 17:47, 17 August 2010 (UTC)
thread_title:  Calculated free energy of native state 

message: Secondary structure prediction section need to be shortened. Currently, it is too long and higly redundant with [] Hsp90 (talk) 09:19, 27 October 2014 (UTC)
thread_title: TODO

message: Is the statement/implication that I added correct, that the non-polarity of the (normally polar) amino acids in an alpha and beta secondary structure?  I'm guessing that's a correct interpretation of what it said about the polarity changes, but is that always true?  I.e. are their "regular cases" where, say, a beta sheet will be close to another residue(s) in the protein which will "deform" the sheet in some way (creating a "bump" in an otherwise "smooth" sheet?)  Note that this is my first reading of the article, and I'm basically making clarifications based on my own understanding "easier" (if one were going to read this article as section from a textbook - which would probably be much more useful - anyone have a suggestion for a good "protein structure/folding" textbook?). Jimw338 (talk) 20:09, 9 March 2015 (UTC)
thread_title:  Non-polarity as 'reason' for sheets/helices 

message: Substituted at 03:29, 30 April 2016 (UTC)
thread_title: Assessment comment

message: Should Deepmind/Google's new algorithm be it's own section about such inference from CS?72.174.71.134 (talk) 09:45, 4 December 2020 (UTC)
replies: text: Yes, but this should be probably a more general section about using "deep learning" and other similar methods. Welcome to contribute. My very best wishes (talk) 00:19, 30 December 2020 (UTC)
thread_title:  AlphaFold