Genereate ensemble of different protonation states cxcalc

User 187e4c3b19

24-05-2011 14:00:58


I was using cxcalc for the generation of ensembles of reasonable protonation states of compounds for a certain pH range. So far, I could not figure out a way to do that in a staight forward manner. Because I would like to do this task for thousands or millons of compounds, I cannot do it with the GUI. I could automize the GUI, but I would rather tent do circumvent it and do it on a command line basis.

Is there a protocol to efficiently generate such an ensemble that saves the 3D structure.

Starting from a smiles string or a 3D structure of a compound, I would like to end up with a file with energy minimized 3D structures, that containes the compound in all protonation states that occure with a certain probability -- e.g. +80% -- at a certain pH, or alternatively in a certain pH range.

kind regards


ChemAxon e08c317633

25-05-2011 14:50:58

This can be done with cxcalc command line application.

1. Create the major microspecies (major protonation state) of molecule at a given pH:

$ cxcalc majorms -H 11 demo10.sdf
id major-ms
1 CC1=CC(=O)C=CC1=O
2 S(SC1=NC2=CC=CC=C2S1)C1=NC2=CC=CC=C2S1
3 [O-]C1=C(Cl)C=C(C=C1N(=O)=O)N(=O)=O
4 N=C1[N-]C=C(S1)N(=O)=O
5 NC1=CC2=C(C=C1)C(=O)C1=C(C=CC=C1)C2=O
6 [O-]C(=O)C1=C(C=CC=C1)C1=C2C=CC(=O)C(Br)=C2OC2=C1C=CC([O-])=C2Br
7 CN(C)C1=C(Cl)C(=O)C2=C(C=CC=C2)C1=O
8 CC1=C(C2=C(C=C1)C(=O)C1=CC=CC=C1C2=O)N(=O)=O
9 CC(=NO)C(C)=N[O-]
10 C1=CC=C(C=C1)P(C1=CC=CC=C1)C1=CC=CC=C1

Same at pH 7.4, the output is wirtten to out1.sdf  SDF file.

cxcalc -o out1.sdf majorms -H 7.4 demo10.sdf -f sdf

2. Create lowest energy 3D conformers from the previously created major microspecies:

cxcalc -o out2.sdf leconformer out1.sdf -f sdf

The output file (out2.sdf) contains the lowest energy 3D structures of major microspecies taken from out1.sdf file.

On unix/linux system the two steps can be performed together using pipes:

cxcalc majorms -H 7.4 demo10.sdf -f sdf | cxcalc -o out.sdf leconformer

Input can be in any file format we support. I used sdf in the example, but it can be also SMILES.


User 187e4c3b19

26-05-2011 09:00:35

Terrific! What happen, when two different protonation states with roughly the same probability occur?

e.g. three possible states with 51%, 48% and 1% probability at a certain pH.

As I understood, the major-ms would generate the state according to 51%.

It is possible to generate an ensemble of structures, that occur with e.g. more than 20% OR more than 0% at least?




ChemAxon e08c317633

30-05-2011 12:10:07

"majorms" calculation returns the microspecies with the highest distribution. E. g. if there are microspecies with distributions 45%, 35%, 20%, then it will return the microspecies with 45% distibution.

"microspeciesdistribution" calculation calculates the microspecies distribution. It returns the list of microspecies  with distributions at given pH.


cxcalc microspeciesdistribution --pH 4.0 input.sdf