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Type Python Script
Author(s) Troels E. Linnet
License BSD
This code has been put under version control in the project Pymol-script-repo


This script is an experimental surface cysteine pKa predictor.
The script is solely based on the work by:

Predicting Reactivities of Protein Surface Cysteines as Part of a Strategy for Selective Multiple Labeling.
Maik H. Jacob, Dan Amir, Vladimir Ratner, Eugene Gussakowsky, and Elisha Haas.
Biochemistry. Vol 44, p. 13664-13672, doi:10.1021/bi051205t

Questions to the article should be send to Maik Jacob.


The authors Jacob et al. were able to describe a computational algorithm that could predict the reactivity of surface cysteines. The algorithm was based on reaction rates with Ellmans reagent, Riddles et al.], on 26 single cysteine mutants of adenylate kinase. The authors could predict the reactivity of the cysteines with a pearson correlation coe�cient of 0.92. The algorithm was based on predicting the pKa values of cysteines by a calculation of electrostatic interactions to the backbone and sidechains of the protein and a energetic solvation effect from the number of atom neighbours. The algorithm is diff�erent from other pKa algorithms, since it calculates a Boltzmann energy distribution for the rotational states of cysteine. The reaction rate with Ellman's reagent was set proportional to the fraction of negatively charged cysteines, Bulaj et al.

Algorithm development

The algorithm is based on electrostatic calculations, where some parameters have been fine-tuned.
The distance from the sulphur atom (SG) of the cysteine to the nearest backbone amide groups and residues with a partial charge, is considered in the electrostatic model.
The model is including a evalution of Boltzman distribution of the rotation of the SG atom around the CA->CB bond.

Twenty-six mutants of Escherichia coli adenylate kinase (4AKE) were produced, each containing a single cysteine at the protein surface, and the rates of the reaction with Ellman's reagent were measured. The reaction rate was set proportional to the pKa, to fine-tune the parameters in the electro static model.

Correction to article

There is a type error in equation 6. There is missing a minus "-". The equations should read:

Example of use

Escherichia coli adenylate kinase.

import cyspka

fetch 4AKE, async=0
create 4AKE-A, /4AKE//A and not resn HOH
delete 4AKE
hide everything
show cartoon, 4AKE-A
cyspka 4AKE-A, A, 18

### You can loop over several residues. 
loopcyspka 4AKE-A, A, residue=18.25.41-42

### OR for the original 26 residues. Takes a long time, so not to many at the time.
#loopcyspka 4AKE-A, A, residue=18.25.41-


  • Ellman's Reagent: 5,5'-Dithiobis(2-nitrobenzoic Acid) a Reexamination. Peter W. Riddles, Robert L. Blakeley, and Burt Zerner

. Analytical Biochemistry. Vol 94, p. 75-81, 1979