Cyspka

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

Introduction

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.

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:
W_MC,SC(i) )= -1*( ΣW_MC(i) + ΣW_SC(i) )

Example of use

Escherichia coli adenylate kinase.

reinitialize
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=18.25.41-42.55.73.90.113.162.188-189.203.28.58.75.102.138.142.148.154.169.214.3.24.86.109

References

• Title of reference. Author name. Journal name. Vol 08/12/2012, p. 54, fig. 5 doi:10.1016/0301-0104(89)87019-3