Affect of adjacent amino acids on pKa values

[James D]

Hello,

I use some standard tables of amino acids pKa values, as the one here:
http://www.cem.msu.edu/~cem252/sp97/ch24/ch24aa.html
and I am especially interested in the pKr (i.e. pKa of the side chains).

Correct me if I'm wrong, but pKa values listed in such tables refer to a "free" peptide, as opposed to a peptide which is a part of a polypeptide.

What I am interested in is to get some intuition as to how might pKr values change when the peptide is a part of a polypeptide. For example, if the peptide in interest is X and its "standard" pKr value is Y, do you expect this pKr value to be higher or lower when X is found in a polypeptide next to some amino acid Z?

I am not looking for exact calculation, but just some thumb rules or intuition.

Thanks,
James

 

[chemisttree]

Just so you know... a peptide and an amino acid are not interchangeable. The table you referenced is for the individual amino acids. Peptides are short chains composed of amino acids and proteins (polypeptides) are longer ones.

The 3-D structure of the protein affects the pKa of the side chains as well as groups nearby (in space). Nearby groups need not be adjacent to the side chain of interest to exert their effect but I would imagine that they would be the most important. I don't believe there are any general rules of thumb for this unless you know of some rules of thumb that one could use to determine 3-D structures for given proteins.

http://enzyme.ucd.ie/main/index.php/Software" might help...

 

[quicknote]

Hello James,

Thank you for your question. I understand your curiosity about the effect of adjacent amino acids on pKa values. The pKa values listed in standard tables do indeed refer to a "free" peptide, and it is important to keep in mind that this value may change when the peptide is part of a polypeptide.

The pKa value of an amino acid side chain can be affected by several factors, including neighboring amino acids, pH, and the overall structure of the polypeptide. For example, the presence of charged amino acids nearby can influence the pKa value of an adjacent amino acid. This is because charged amino acids can create a polar environment, which can stabilize or destabilize the ionization of nearby amino acids.

In general, the pKa value of an amino acid side chain can be affected by its interactions with other amino acids in the polypeptide. For example, if an amino acid with a high pKa value is surrounded by amino acids with low pKa values, it may become more acidic due to the stabilizing effect of the surrounding amino acids. On the other hand, if an amino acid with a low pKa value is surrounded by amino acids with high pKa values, it may become more basic.

It is difficult to predict the exact change in pKa value without specific calculations or experiments, but as a general rule, the presence of charged or polar amino acids nearby can affect the pKa value of an adjacent amino acid. I hope this helps provide some intuition for your research.

Best,