The (human) genetic code encodes 20 amino acids. They form a protein using peptide bonds. Each amino acid has a carboxyl group (COOH) and an amino group (NH2) that can potentially form a peptide bond.

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Source: The Culture of Chemistry

Does this property of amino acids means that each amino acid can form a peptide bond in any combination? In other words, are there certain amino acid doublets in existence that never pair up?

  • $\begingroup$ Welcome to Biology S.E.! If you need additional assistance, please visit The Help Center. $\endgroup$
    – L.B.
    Mar 21, 2015 at 17:26
  • $\begingroup$ Right, so any amino acids may be chained together. The limitation is that the function of a protein depends on which amino acids are in your polypeptide chain, and in what order. The cell mediates this on multiple levels: en.wikipedia.org/wiki/Protein $\endgroup$
    – CKM
    Mar 21, 2015 at 17:54
  • $\begingroup$ Exactly what is the question? Whether all amino acids are "compatible"? $\endgroup$ Mar 24, 2015 at 9:53
  • $\begingroup$ I edited the question to prevent closure. I think it is a valid question with enough background. It was just formulated a bit unclear $\endgroup$
    – AliceD
    Mar 24, 2015 at 11:22

3 Answers 3


It seems like you may be thinking along the lines of DNA, where adenine pairs only with thymine and guanine with cytosine.

Unlike DNA, amino acid chains are single-stranded...example chain of amino acids, aka a polypeptide chain

...so there is no pairing of compatible types like there is in DNA. Neighboring amino acids in the chain can be in any combination (as you say, because each has a carboxyl group and an amino acid group), just as neighboring nucleotides in DNA (ie those next to, not across from, each other) can come in any order.

In practical terms, the functional groups of amino acids have different chemical properties (hydrophobic, hydrophilic, aromatic), therefore some pairings are probably more commonly found than others. But in principle there is no restriction on who is next to who.


Short answer: there are no restrictions in principle on which amino acids can follow which. That means that in principle you can have polypeptide in any configuration: AAAA, WQWQWQ etc.

Problem is that polypeptides must be functional and, because they are in aqueous solution, it puts restrictions on how polypeptide form secondary and tertiary structure. It means that having very rigid hydrophobic surface is energetically unfavorable. If cell where to produce such polypeptide, it might be either degraded or cause problems for cell, such as aggregates or other form of toxicity.

That means that polypeptides has more restrictions than just linkage (C-N bonding) order. And of course it has been studied: Probabilistic analysis of the frequencies of amino acid pairs within characterized protein sequences.

Authors analyzed protein databases to find out which doublets of amino acids are more and less common. First of all, not all amino acids (of which there are 20 considered) have same occurrence, e.g. P(L, leucine)=0.096, P(W, tryptophan)=0.0118.

And, of course, not doublets are equally distributed (16 pairs out of 400 were picked as statistically significant):

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  • $\begingroup$ I think this is the better answer. $\endgroup$
    – inf3rno
    May 13, 2015 at 7:31

To answer your question: No, there are no restrictions to what amino acid is next ("a nearest neighbor") to its N-terminal or C-terminal neighbor.


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