I'm struggling a bit in Bio 111 with confusing terminology between the terms "chain" and "molecule". I understand the primary structure of a protein is a chain of amino acids connected by peptide (covalent) bonds - easily a molecule. And the secondary helix structure could be a single molecule/polypeptide chain. Up to this point, chain = molecule. But a beta-pleated secondary structure would have to be two or more chains (molecules) connected by hydrogen bonds. No? Or is a beta-pleated sheet considered one molecule? One chain?

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    $\begingroup$ beta pleats can still be a single chain and molecule, don't forget proteins fold which ba bring distant portion of the ame chain together. $\endgroup$ – John Jun 23 '18 at 4:17
  • $\begingroup$ Thanks John. But I think beta-pleated sheets must, by definition, be multiple molecules if you accept that a molecule is defined as consisting of only covalent bonds. I think I finally pieced the different terms together and cam up with definitions that work. I sure would like confirmation from anyone more knowledgable. $\endgroup$ – Byron1948 Jun 23 '18 at 15:44
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    $\begingroup$ I think you are confused about what a beta-pleated sheet is, the secondary structure of a pleated sheet can and usually is made from a single amino acid chain. d1yboe6750e2cu.cloudfront.net/i/… $\endgroup$ – John Jun 23 '18 at 15:47
  • $\begingroup$ Chain yes. But a beta-pleated sheet has polypeptide chains connected "head" (carboxyl) to tail in alternating directions according to the definition of Secondary Structure in my textbook. That being the case, the head-to-tail binding can only be hydrogen bonding - much like the pairs of strands (molecules) of DNA in a helix. And if molecules only contain covalent or ionic bonds, then the beta-pleated sheet may be one chain but it is multiple molecules. $\endgroup$ – Byron1948 Jun 23 '18 at 16:11
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    $\begingroup$ no look at the image I linked it is a single chain, covalent bonds all the way through, that folds back on itself forming additional hydrogen bonds. DNA is the wrong analogy RNA which can fold back on itself and link is a better comparison. Here is another even better illustration. upload.wikimedia.org/wikipedia/commons/thumb/1/10/… $\endgroup$ – John Jun 23 '18 at 16:25

This sort of question is easily answered by consulting and carefully reading an introductory biochemistry text, like this section of Berg et al. on line. However, as the diagrams of β-sheets can be confusing, I will summarize.

  • The amino acids linked by covalent peptide bonds produce a protein molecule in the form of a single polypeptide chain.
  • This polypeptide chain folds into a specific shape in three-dimensional space, its conformation being maintained by weak non-covalent interactions — ionic bonds, hydrogen bonds and Van der Walls interactions. (Often referred to as protein tertiary structure.) Proteins that have a roughly spheroidal shape (rather than being long and extended) are referred to as globular proteins.
  • Often the three-dimensional structure has large regular components (often referred to as secondary structure) because of the potential for repeated hydrogen bonding between the CO and NH of the repeating peptide bonds.

Molecular diagrams to illustrate the type of secondary structure known as the β-sheet generally show just a section of the polypeptide chain for clarity, as in the left-hand illustration from Berg et al., below:

Protein secondary structure

This may give the impression that two separate chains are involved†, but cartoon representations such as the one on the right (also from the same section of Berg et al.) show that for globular proteins this is not so.

In the diagram the flat blue arrows represent β-strands that are hydrogen-bonded to one another to form a twisted barrel-shaped β-sheet. The yellow ‘rope’ between the arrows represents the continuation of the chain in the non-sheet areas of the structure.

So the possibility for confusion arises primarily from the difficulty of showing the detailed pattern of hydrogen bonding in the whole of a large protein. (Although it may also arise from the fact that it is easiest to illustrate β-sheets using the diagrams of silk fibroin — historically the first to be described — in which the sheets are very regular and flat. To an extent this is misleading as the right-hand side of my diagram indicates.)


Fibrous proteins, such as silk, exist in which β-sheets are formed between many different chains. The identification of the individual chains can be made unequivocally, e.g. on the basis of the gene sequence, and it is clear that the higher-order structure is composed of many individual molecules. In smaller higher-order structures, e.g. tetramers of globular proteins held together by weak non-covalent interactions, the semantic question of whether a molecule can be made up of several individual chains arises. In my opinion, this question is best ignored, unless one is studying the biophysical chemistry of proteins.

  • $\begingroup$ Well David, as it happens, my question is a result of taking Bio 111 in college right now. Our Pearson textbook doesn't show the ends of the polypeptide chains in the illustration of secondary structures. The illustration on the left in your answer would have provided great insight but doesn't explain the fact that proteins are called "molecules" in other parts of the text. The consensus I'm receiving is that there is no clear consensus on the definition of "molecule" with respect to bonding. Everyone does agree that hydrogen bonds between water molecules do not make all of them one molecule. $\endgroup$ – Byron1948 Jun 27 '18 at 16:23
  • $\begingroup$ My answer assumed that you were taking an introductory course which included something about proteins, and this was likely to be dealing predominantly with globular proteins. If there is any aspect of it that is unclear or which you dispute, please tell me. As regards the meaning of the word molecule in relation to proteins in general, this is another question and concerns mainly higher order structures. If this really interests you, please ask it as a separate question. However, of one thing there is no doubt: the polypeptide chain translated from a mRNA encoded by a gene, is a molecule. $\endgroup$ – David Jun 27 '18 at 18:07
  • $\begingroup$ @Byron1948 your question is a natural one for someone approaching protein structure after some chemistry. Has David answered your question? Do you see that the atoms in the $\beta$-pleated sheet are in fact all connected by covalent bonds (in addition to hydrogen bonds); that the molecule is just long and flexible enough that more than one type of interaction can be involved? $\endgroup$ – De Novo Jun 27 '18 at 19:53
  • $\begingroup$ Thanks Dan. No, I don't think I have a clear answer yet. The illustration on the left of David's first comment show hydrogen bonds a the ends of the polypeptide chains (the dotted lines). I'm looking for a definition of molecule in terms of bonding. If the definition is "multiple atoms bonded together", then fine. Technically all water in a drop is one molecule due to hydrogen bonds. But this doesn't sound like a reasonable definition to me. What am I missing? $\endgroup$ – Byron1948 Jun 28 '18 at 22:15
  • $\begingroup$ @Byron1948 — Your question related to text book diagrams of beta-sheets of proteins, leading to the statement: "But a beta-pleated secondary structure would have to be two or more chains (molecules) connected by hydrogen bonds. No?" My answer was "No" — the diagram (unless it stated it was silk fibroin) represented hydrogen bonds between parts of a single polypeptide chain (and not at the ends, as you state). If you want to discuss the meaning of the term "molecule" start with Chemistry SE. Ask separately about protein molecules here when you are more familiar with different proteins. $\endgroup$ – David Jun 29 '18 at 8:48

This may be of additional help, as I used to struggle with the difference between a peptide and a protein too.

A peptide is a single, short chain of amino acids (approx. <50 amino acid length). It's a single molecule.

A protein may or may not be a single chain of amino acids. It may or may not be a single molecule, it could be several molecules adhering to each other.

Hemoglobin is a protein. It's constituents, alpha- and beta-globin, are peptides. It's correct to refer to each of them as proteins, too. Alpha-globin is definitely a protein. What you would never say, however, is that "the hemoglobin protein is composed of four proteins", two alpha-globin and two beta-globin proteins, even though it is most certainly technically correct.

If you want to be extremely pedantic, hemoglobin is a single (metallo)protein composed of four peptide molecules, which behaves as a single unit, hence why it can be colloquially but not strictly referred to as a molecule.

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    $\begingroup$ This is not completely right. A peptide is seen as a short chain of amino acids linked together. More complex proteins are referred to as polypeptides. Today, proteins are seen as the functional unit built from polypeptides or peptides - sometimes more than one. But a protein can also consist of a single polypeptide. What matters here is the 3D-structure. $\endgroup$ – Chris Jun 26 '18 at 11:57
  • $\begingroup$ I don't understand how this disagrees with what I wrote. It's exactly re-written. Polypeptides are multiple peptides, hence 'poly'. Proteins are either peptides or polypeptides. Peptides are arbitrarily "short" single chains. Which part is not right? $\endgroup$ – S Pr Jul 5 '18 at 10:02
  • $\begingroup$ Peptides are explicitly short - not only a single chain. $\endgroup$ – Chris Jul 5 '18 at 12:59
  • $\begingroup$ I've updated my answer. 20 years ago I was taught (and older generation scientists) say that a peptide is <100 AAs long. Wikipedia states <50. I guess it's arbitrary and fashion-sensitive, but we can agree it's a "short" chain. $\endgroup$ – S Pr Jul 12 '18 at 10:08

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