I was pinged this weekend by Zsolt Zsoldos of the SimBioSys Blog about us having duplicates of certain amino acids of ChemSpider. He commented that there were a series of structures showing up for a search based on identifier:

Aspartic acid: 411 and 5745
Arginine: 227 , 6082 , 64224 , 1266045
Histidine: 752 , 6038 , 64237 , 4450698

Welcome to our world! So, let’s start with aspartic acid. What IS the structure of aspartic acid? Is it the one on Wikipedia here? The one labeled with the S stereochemistry but showing no stereobonds (will be resolved in the curation process of Wikipedia structures!). Is aspartic acid the deprotonated version? Well, it depends on who you ask and also who is depositing on our system.

The same is true for arginine where there is a non-stereospecific isomer, a D-isomer, a L-isomer and a charged form. Similarly for Histidine. All are appropriate.

Why is Zsolt interested in this? Because of a conversation he is engaged in…

For the docking community there is a very valuable resource out there called ZINC. They also have a very interesting email discussion list called Zinc-Fans. Recently a post initiated a discussion about protonation states and asking the question:

“In a certain docking protocol, my concern is primarily of the protonation states of the ligands in the library (subsets with different pH ranges) downloaded from ZINC, as I have recently read an article on “The influence of protonation in protein-ligand docking”


Considering an enzyme that is reported to be optimum at a pH of 7.6-8.0, which we intend to find inhibitors for, which subset of ZINC compounds do Ichose for docking against my target of interest?”

Zsolt came searching ChemSpider for the amino acid structures and found the complexities in terms of charged/stereo forms. But his postinf regarding the “Correct Protonation State for Docking” was an education in itself. If you are engaged in docking experiments at all this is likely a must read. For the rest of us neophytes it’s education!

Stumble it!

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