Calculating pKa values with mm scp

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MM_SCP is a computational method of calculating pH dependent electrostatic effects, including the pKa of individual residues of entire proteins. It was developed by Ernie Mehler, a member of the Department of Physiology and Biophysics.

The program performs a titration of each residue, and reports the pKa based on the titration curve.

Contents

Performing a pKa computational run

To calculate the pKa for each residue in a protein using mm_scp, you will need:

  • A protein's PDB file
  • The mm_scp binaries
  • A working copy of CHARMM
  • The parameter files and scripts available here: ~mjw/sno_positive

The pipeline

The pipeline takes place in 4 stages:

1. PDB cutting

Run the step1.sh script:

./step1 <PDBNAME> <CHAIN>

This prepares a new PDB file (entitled <PDBNAME>_cut.pdb, including only the chain of interest.

2. CHARMM preparation

The .con and .crd files for the CHARMM minimization are then generated, using step2.sh.

./step2.sh <PDBNAME>

The .seq file is the generated:

./step3.sh <PDBNAME>

3. CHARMM run

All files should be named in lower case, before attempting a CHARMM run!

Replace the PDBNAME variable in buildp.template file with the PDB accession code. Then perform a CHARMM run:

charmm < buildp.inp

Assuming all went well, you should have an updated .crd file which can be used with the mm_scp code. You should replace all CYS residue types in the .crd file with the titratable form, CYD.

4. The mm_scp run

Finally, replace the variables PDBNAME and NUM in the mm_scp input file with the PDB accession code and number of residues (in the seq file), and a mm_scp run can be performed:

./mm_scp < input.inp

5. Parsing the output

The output contains information for each titratable residue in the original PDB file, at each successive pH titration iteration. These values can be used to plot tiration curves. The final pKa value can be found towards the bottom of the file, in a column labelled 'pk 1/2'.

mm_scp data

The data, programs and input files used to perform these runs can be found in ~mjw/sno_positive on beech.

pKa results

Footnotes

"Titration iteration" is a great name for a ska band.

Links

mm_scp web site</pre>

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