# Difference between revisions of "Cyspka"

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=== Correction to article === | === Correction to article === | ||

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

− | + | <math> | |

+ | W_{MC,SC(i)} = - \left( \sum W_{MC(i)} + \sum W_{SC(i)} \right) | ||

+ | </math> | ||

== Example of use == | == Example of use == |

## Revision as of 18:03, 13 January 2012

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 |

## Contents

## 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.

### Overview

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.

```
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

*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

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