Talk:Protein folding

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"misfolded (incorrectly folded)"[edit]

Is this really necessary? Most people know what the prefix "mis" means. —Preceding unsigned comment added by (talk) 17:03, 23 November 2010 (UTC)

Remove Dual Polarization Interferometry?[edit]

This is a relatively obscure technique with little to do with protein folding. Only 39 articles on Pubmed deal with DPI and only 2 of these deal loosely with protein folding. By comparison, there are 3138 using NMR which is not discussed in the article. Also, the text seems to be taken verbatim from the DPI article --Biophysik (talk) 04:51, 4 May 2009 (UTC)

Most protein folding occurs in the ER lumen, and I think this article implies it happens in the cytosol, which is a very different environment. Can someone back me up here? I think it should be changed. —Preceding unsigned comment added by (talk) 15:45, 29 September 2008 (UTC)

This is just a feedback: the link for the third reference,

Jeremy M. Berg, John L. Tymoczko, Lubert Stryer; Web content by Neil D. Clarke (2002). "3. Protein Structure and Function", Biochemistry. San Francisco: W.H. Freeman. ISBN 0-7167-4684-0.

does not work. Delete this comment when solved. —Preceding unsigned comment added by (talk) 09:43, 13 August 2008 (UTC)

Is there a way to simplify the explanation of the process? The 'middle-school English' explanation (which of course, has since been deleted)was actually a good summary without having to go deep into the complexity.

I'm not sure my biochemistry is up to it, but should something about the different levels of protein structure be added here, (primary, secondary, tertitary etc.)?

The main protein article has that - I suppose you could refer to that article. -- Marj 05:44, 26 Oct 2003 (UTC) ok

I've tried to make the initial section a bit clearer but it's a difficult thing to provide a non-technical summary of. I've also put in some references to (mostly) free articles & books. Hopefully it doesn't jump in quite so quickly now. See what you think. MockAE 12:34, 14 April 2007 (UTC)

Folding temperature[edit]

I have read that the folding temperature of a protein is defined as the temperature at which there is a peak in the heat capacity of the protein. I am not sure what this means physically about what is different in the protein at the folding temperature versus below the folding temperature. However, I would like very much to know. Thank you. —Preceding unsigned comment added by Shindizzle (talkcontribs)

This page is useless. If anyone could understand this page, they wouldn't need Wikipedia to explain it to them. —Preceding unsigned comment added by (talk)

The folding temperature is a minor point in the grand scheme of protein folding. FYI, it is a characteristic temperature at which the protein spends half the time in the folded state and half the time in the unfolded state. The peak of the heat capacity for any substance (protein or otherwise) is the temperature at which the transition from one state to another occurs (e.g. phase transition). So, for proteins, the peak is the temperature at which the protein goes from the unfolded state to the folded state. —Preceding unsigned comment added by (talk)

That's not entirely correct. The temperature at which the protein spends half the time in the folded state and half the time in the unfolded state is the ' folding transition temperature for a two state folding protein '. The term 'folding temperature' is an imprecise term. -- (talk) 15:41, 10 March 2008 (UTC)

external link to rosetta is needless- they do not study the protein folding. they predict final structure, ant this should be addressed to "protein structure prediction" . this also refers to human proteom folding project, predictor at home, fight aids at home and all others. only Stanford is studying the protein folding. 12:30, 8 May 2006 (UTC)Samurajus712

H-bonds, entropy, etc.[edit]

This is a nice article, although it could be done more "in depth". H-bonds do stabilize protein structure. The catch: water is liquid. When water freezes itself, there is a certain energy gain called enthalpy of fusion. This enthalpy of fusion originates mostly from formation of H-bonds between molecules of water: these H-bonds are strong in the solid state, but "transient" in the liquid mobile water. Same thing with protein folding, helix-coil transitions, crystallization, etc. The energy of H-bond in protein folding is ~-1.5 kcal/mol (mutagenesis and other data). Main force that opposes protein folding is conformational entropy (like in any other liquid to solid state type transition). This is easy to fix. I can do this later. Biophys 17:26, 28 October 2006 (UTC)

Techniques for studying protein folding[edit]

It would be good to separate experimental and computational techniques. There are many more experimental methods that should be mentioned here. Biophys 18:03, 29 October 2006 (UTC)

I noticed this also. It seems that there is a lack of flow and continuity in this section. The first three methods mentioned are experimental, then the article talks about computational methods, and finally switches back to experimental methods. If it's alright I'm going to clean this up.Dopeytaylor (talk) 18:03, 14 March 2011 (UTC)
I have reorganized this section, splitting it into two, and reordering a few things. I'm still not satisfied with it. (Dopeytaylor (talk) 18:09, 14 March 2011 (UTC)

It is important to tell something about protein folding pathways based on experimental data (intermediates, transition states, etc.), about thermodynamic stability of proteins, and differences between water-soluble and transmembrane proteins. Beta-sheet is not a secondary structure! The beta-strand is. Biophys 04:08, 2 November 2006 (UTC)

Disulfide bonds often exist within beta sheets, and sometimes even within alpha helices. This is corrected. Biophys 02:07, 4 November 2006 (UTC)

Random coil --> Random coil (protein folding)[edit]

Does anyone else think it might be useful to split the random coil article into 2 separate articles? With the first being used to describe the mathematical theory, and the second to describe the protein related aspects of the model?-- (talk) 18:32, 30 December 2007 (UTC)

Another useful study[edit]

The following paper may contain useful material for this article:

Igor V. Grigoriev; Sung-Hou Kim. Detection of Protein Fold Similarity Based on Correlation of Amino Acid Properties. Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 25. (Dec. 7, 1999), pp. 14318-14323. Stable URL: (talk) 19:08, 27 October 2008 (UTC) "Iceberg" protein refolder: In the physical point of view, "ice" is a kind of "pure mineral rock", and it can not growing up at the coexistence of other materials. In the process of freezing, salt is drived out and departs from water. In the refolding process,the Solute, that is denaturant such as urea(density is 1.33) and Guanidine(density is 1.34), is also affected by temperature. And the density of active protein is around 1, so the protein stay near the solution uper layer. This directly leads to a decline of the denaturant concentration in the solution. Thus, we obtain two “reductions”- the reduction of thermal movement (this can greatly reduce the probability of peptides entanglement) and the reduction of denaturant concentration at the same time—the two most essential conditions in protein refolding. This creates an excellent condition for protein refolding, that is, low-temperature and a smooth decline in denaturant gradient. Taking the physical and chemical properties of peptide into consideration, the two terminals of the chain are carrying different charges ( N-terminal charge is positive, while C-terminal charge is negative). This enables us to use a program-controlled high voltage electric field to adjust peptides’ state in the solution, to restrict their movement, to pull peptide into a "orderly queue" and to prevent peptides from mutual entangling. At the same time this instrment does not exclude any other existing method of protein folding, and can be merged with the existing ways of folding easily, improve the efficiency and reduce the cost of refolding.

2. Freeze-dry protein folding method: this protocol is only suit for those kind of proteins which can be made in frozen powder or cold resistable proteins(such as EGF, IGF).

 1. freeze-dry machine 
 2. 8M urea, 10mM pH8 phosphate buffer, 5mM BME, inclusion body solution, 25 centigrade overnight
 3. Add sucrose 6% weight or other addictives as freezing protection
 4. Standard process freeze-dry the solution
 5. Use wind, high voltage electrostatic way, or little brush to separate the protein powder and the crystal(keep the room humidity low)  
 6. Test the activity  —Preceding unsigned comment added by Hawk 0917 (talkcontribs) 13:00, 2 July 2009 (UTC) 

Evolutionary Aspects of Protein Folding[edit]

It would be helpful to discuss the evolutionary aspects of protein folding as well —Preceding unsigned comment added by (talk) 15:45, 1 November 2008 (UTC)

Someone care to explain 'why' people do protein folding? There seems to be a whole lot of information about 'how' but not 'why. —Preceding unsigned comment added by (talk) 11:59, 14 June 2009 (UTC)

Incorrect protein folding and neurodegenerative disease[edit]

Should we realy have at the end of this section a list of all important scientists who are involved in this research!?--Gilisa (talk) 11:20, 5 November 2009 (UTC)

I agree that it doesn't make much sense. The same goes for the section "Modern studies of folding with high time resolution". It would be better to provide one or two review articles referencing the same authors at the respective sections. -- Mittinatten (talk) 13:49, 11 November 2009 (UTC)

I removed the names of scientist and added two review articles that I like, maybe we could add more. -- Mittinatten (talk) 20:27, 17 December 2009 (UTC)

"Proving" and "disproving" Anfinsen hypothesis[edit]

The following segment seems to be very problematic:

In the seminal research work published nearly four decades ago, C.B. Anfinsen hypothesized that "information dictating the native fold of protein domains is encoded in their amino acid sequence" [1]. However, with the explosive amount of protein sequence, structure, and fold data generated since the time of Anfinsen during the omics era, the emerging picture of the protein universe has challenged Anfinsen's dogma, for it has become evident that numerous protein folds have incredible sequence diversity with no consistent "fold code" [2]. In support of this observation, recent studies have shown that proteins with as low as 1-2% sequence identity may still adopt the same native fold, thus defying any tangible encoding of fold-dictating information into protein sequence [3]. The pursuit of the elusive "fold code" has resulted in little more than patterns of amino acid sequence conservations specific to certain proteins, but no finding has been compelling enough to generalize universally or to utilize for biological applications [4].

In a recent study, scientists from Harvard-MIT have shown that, despite the enormous diversity within protein folds at the level of 1-dimensional amino acid sequence, nature has encoded fold-conserved information at higher dimensions of protein space such as the 2-D (protein contact maps) or 3-D (structure), that are known to be more intricately related to protein folding phenomena [5]. The study published in PLoS ONE illuminated latent fold-conserved information from higher dimensional protein space using network theory approaches. By examining the entire protein universe on a fold-by-fold basis, the study revealed that atomic interaction networks in the solvent-unexposed core of protein domains are fold-conserved and unique to each protein's native fold, thus appearing to be the encoded "signature" of protein domains. This study hence uncovered that the protein fold code is a "network phenomena" in addition to a sequence and structural phenomena as commonly presumed. The discovery of such a protein folding code also confirms Anfinsens Dogma by proving that a significant portion of the fold-dictating information is encoded by the atomic interaction network in the solvent-unexposed core of protein domains.

  • Unfortunately, none of the quoted publications actually proves or disproves Anfinsen hypothesis, but tells about unrelated subjects, such as the same "fold" (do not mix with "folding") being encoded by different amino acid sequences, and so on.Biophys (talk) 22:32, 30 June 2010 (UTC)

Disordered Proteins[edit]

I take issue with the fact that this article seems to assume that all proteins fold into a well defined 3D shape. There are many instances where it is known that large portions of a protein are disordered, or dynamic in their shape. I believe there either needs to be a segment added on "Disordered Proteins". If need be I can help track down citations. Dopeytaylor (talk) 04:05, 15 February 2011 (UTC)

Sure, please see Intrinsically unstructured proteins. Biophys (talk) 05:54, 15 February 2011 (UTC)
Thanks, I see the link in the opening paragraphs of the article now. I think it is enough to satisfy me.Dopeytaylor (talk) 16:45, 14 March 2011 (UTC)
Actually, I still have a problem with the sentence that mentions disorder proteins. The sentence states “The correct three-dimensional structure is essential to function, although some parts of functional proteins may remain unfolded ”. I believe many biologists, including myself might, disagree with the notion that, for a protein, or part of a protein to function, it must always have a distinct static three dimensional structure. Performing a quick search I can find at least two papers where it is stated that a functionally important region of a protein is intrinsically disordered.
A Structurally Disordered Region at the C Terminus of Capsid Plays Essential Roles in Multimerization and Membrane Binding of the Gag Protein of Human Immunodeficiency Virus Type 1
Structure of the Dual Enzyme Ire1 Reveals the Basis for Catalysis and Regulation in Nonconventional RNA Splicing

Dopeytaylor (talk) 18:45, 29 March 2011 (UTC)

Experimental techniques for studying protein folding[edit]

I noticed that there are no citations for any of the methods used to study protein folding. It is well known that NMR is used to study structure, but I believe that studying folding using NMR is a special case, and warrants at least a few citations. The same goes for the other methods. Can we find some citations where a paper reports details about the steps a protein goes through when folding that have been discovered using the respective method?

I believe this section is also missing what I've always thought was a very important method for studying folding, and thats point wise mutation studies. I think the most common one cited for this the the Fersht study on Barnase. I will add a section on this method. I think this paper might be the best one to cite. if there is a better one, or more, please let me know. Dopeytaylor (talk) 18:59, 29 March 2011 (UTC)

Sure, this is publication by Fersht about Phi value analysis. Phi value analysis should be described in this article in more detail.Hodja Nasreddin (talk) 02:02, 30 March 2011 (UTC)

Good reference material: "The Protein-Folding Problem, 50 Years On"[edit]

Anyone who is interested in improving this article should probably look at the review article The Protein-Folding Problem, 50 Years On. Fairly straightforward read, and it contains a lot of up-to-date and useful information. • Jesse V.(talk) 05:40, 27 November 2012 (UTC)

And let's not forget chaperones. Macdonald-ross (talk) 05:53, 21 September 2013 (UTC)

External links modified[edit]

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  1. ^ Anfinsen CB. (20 July 1973). "Principles that Govern the Folding of Protein Chains". Science. 181 (96): 223–230. doi:10.1126/science.181.4096.223. PMID 4124164.  More than one of |number= and |issue= specified (help)
  2. ^ Govindarajan S, Recabarren R, Goldstein RA. (17 Sep 1999). "Estimating the total number of protein folds.". Proteins. 35 (4): 408–414. doi:10.1002/(SICI)1097-0134(19990601)35:4<408::AID-PROT4>3.0.CO;2-A. PMID 10382668.  Text "PMID: 10382668" ignored (help)
  3. ^ Mirny, L. A., Abkevich, V. I. & Shakhnovich, E. I. (28 Apr 1998). "How evolution makes proteins fold quickly.". Proc Natl Acad Sci U S A. 95 (9): 4976–4981. doi:10.1073/pnas.95.9.4976. PMC 20198. PMID 9560213.  Text "PMID: 9560213" ignored (help); More than one of |number= and |issue= specified (help)
  4. ^ S Rackovsky. (15 Jan 1993). "On the nature of the protein folding code.". Proc Natl Acad Sci U S A. 90 (2): 644–648. doi:10.1073/pnas.90.2.644. PMC 45720. PMID 8421700.  Text "PMCID: PMC45720" ignored (help); More than one of |number= and |issue= specified (help)
  5. ^ Venkataramanan Soundararajan, Rahul Raman, S. Raguram, V. Sasisekharan, Ram Sasisekharan (2010). "Atomic Interaction Networks in the Core of Protein Domains and Their Native Folds". PLoS ONE 5 (2): e9391. doi:10.1371/journal.pone.0009391. PMC 2826414. PMID 20186337.  Unknown parameter |pmcid= ignored (|pmc= suggested) (help)