pKa prediction made easy

  

   

  

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Welcome to Karlsberg+, the web interface to continuum electrostatics based pKa prediction. Our method is based on numerical solutions of the linearized Poisson-Boltzmann equation (LPBE) in combination with structural relaxation of hydrogens and salt bridges.

Based on your structure Karlsberg+ will 'predict' hydrogen positions and alternative side chain conformers for ion pairs present in salt bridges depending on the bulk pH. After evaluating the relevant electrostatic energies Karlsberg performs a Monte-Carlo sampling of protein protonation patterns and pH adapted conformations.

The approach has been shown to increase the accuracy of LPBE-based pKas without meddling with the protein dielectric constant for which Karlsberg+ uses a constant value of 4.0. Please acknowledge your use of Karlsberg+ by citing:  

  

   

help Please upload a structure in PDB format:  

  

  

  

'HETATM' lines will be ignored. Including crystal waters is possible. NMR structures are supported.  

  

  

  

   

  

  

Kieseritzky G, Knapp EW. Optimizing pKA computation in proteins with pH adapted conformations (PACs). Proteins: Structure, Function, and Bioinformatics 2008; 71:1335-1348  

  

  

  

Rabenstein B, Knapp EW. Calculated pH-Dependent Population and Protonation of Carbon-Monoxy-Myoglobin Conformers. Biophysical Journal 2001;80(3):1141-1150.  

  

  

  

(To reproduce results in the above paper, no initial geometry optimization with GBSW as the solvation model was used.)

Karlsberg+ is based on several programs. Electrostatic energies as obtained by numerical solution of the LPBE are calculated by our own software TAPBS. It is essentially a front end to APBS 1.3 developed by the group of Nathan Baker. TAPBS was made to efficiently automate the repeated evaluation of the LPBE to calculate Born solvation, background and pair wise energy terms of all titratable residues in a protein and adds the functionality of implicit membrane slabs. Webserver calculations are based on TAPBS-0.1. Installation instructions can be found here.

The Monte-Carlo sampling part is done by Karlsberg2 developed by Björn Rabenstein. The previous version Karlsberg1 supported pH and redox titration, parallel-tempering as well as multiple global conformations. Karlsberg2 now also supports multiple charged states and local conformers.

TAPBS and Karlsberg2 are free software and provided here free of charge. If you want to publish data based on these stand-alone programs please cite the papers listed above.