Sunday, February 26, 2012

The PROPKA proposal

It's hard to write a proposal, and I had made several false starts.  To get out of the rut I used a trick I've used before where I make a sort of outline/very condensed version where I focus exclusively on what I want to say rather than how I want to say it. 

Anyway, the trick worked once again, and the proposal was shipped off on Friday - three days before the deadline.  Only this time I wrote the document on blogger and, inspired by Rosie Redfields latest post, I am putting it up on the blog.

Title: Electrostatics in Protein/Nucleic Acid Complexes
Not a very sexy title, but what else?

Extend PROPKA to DNA and RNA and use it to ...?

Background and Significance
pKa Prediction. Proteins contains charged groups that are key to their stability and function.  Assigning correct charges is crucial for rationalizing and modeling protein chemistry.  It is hard to measure these charges, so they have to be computed.  PROPKA is arguably the most popular way of doing this: many users and citations, interface to popular programs such as PDB2PQR and VMD.

Thanks to these efforts protein charges can now be assigned with confidence.  However, picture is different for the other major biomolecules DNA and RNA, and protein-DNA/RNA complexes.

Most pKa prediction programs can only handle proteins. PROPKA is one of the few programs that have been extended to small molecule ligands.  No pKa prediction program has been extended to DNA and RNA (check if that's true?), and this is what is proposed here.

Protein-DNA/RNA complexes. Why are proteins-DNA/RNA complexes important? Why are charged groups important for these complexes?  What complexes will PROPKA be applied to and why these?

Who are involved?  Jan, Mats, PNNL, UIUC,

Research Plan and Methodology
How will PROPKA be modified to handle DNA and RNA? pKmodel values, hydrogen bond strengths,
How will it be validated? What experimental data is there?  Compute pKa values using EFMO.
What systems will it be applied to? What will be computed?

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 Unported License.

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