Calculating pI from structural information rather than sequences

Question

[Joe]

This is a bit of a long shot (both in terms of expecting something to exist, but also given BioStars usual areas of focus), but:

Is anyone aware of an approach (or ideally an existing tool), that will calculate a pI for a protein complex, given that EM density and/or atomic data is available?

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To my mind, the process would probably be something along the lines of the usual electrostatic surface generation algorithms (a 'rolling sphere'), over the whole complex, though I imagine this is not going to be simple to implement, if possible at all.

Answer 1

[Woa]

This article might give you something to start with:

https://www.pnas.org/content/98/22/12473

The first author of the article seems to be active in this research group and possibly can help http://www.northeastern.edu/org/

[Woa]

Also, https://en.wikipedia.org/wiki/Protein_pKa_calculations#Using_the_Poisson%E2%80%93Boltzmann_equation

Answer 2

[Mensur Dlakic]

Barry Honig's group has DelPhi that may give you a starting point. Also APBS.

[Joe]

I had come across both of those, and have been playing with APBS, but they only work for individual proteins (at least as far as I’ve been able to surmise so far).

[Mensur Dlakic]

Fooling a program into thinking that there is one chain instead of two is simple. Delete the TER line between the chains, rename the second chain letter to match the first chain, and renumber second chain residues so there is no overlap. Then it will look like a single chain that is discontinuous, and most programs will treat is as such.

[Joe]

I had considered this too, but the complex in question is very large, and most programs will choke I think. I was wondering mainly if someone had come up with a more generalised approach.

I will give this a try though in the absence of something better - a hack is better than nothing!