Hi Marc –
The earlier response to this thread is correct: I would not include the ions explicitly but instead model their effect through the ionic strength of the Poisson-Boltzmann equation. You may also want to change the limits of the color map for your surface potential visualization – they may need to be increased to make the figure more interpretable.
Pacific Northwest National Laboratory
From: Marc van der Kamp [mailto:email@example.com]
Sent: Thursday, April 12, 2012 6:12 AM
Subject: [apbs-users] electrostatic surface around proteins with non-zero overall charge
I have some questions about (the interpretation of) the electrostatic surface around a protein structure that has a significant non-zero overall charge.
In my specific example, I have taken (energy minimized) structures from MD simulations of a protein. The overall charge on the protein (after assigning the most likely protonation states) is -12 e. In my MD simulations (using explicit solvent and periodic boundary conditions), I include 12 sodium ions to neutralize the system.
After getting .pqr files from the structures obtained from simulation (using the force-field charges), I have used the APBS plugin in PyMOL to generate images of the solvent accessible surface, colored by electrostatic potential (going from -5 kT - in red - to 5 kT - in blue).
I did this for the protein only, and for a structure of the protein + the sodium ions (with positions from the MD simulation + minimization).
Perhaps unsurprisingly, in the first case, the surface is predominantly red (see apbs1.png) - especially in the pocket in the middle of the image. In the second case, with the sodium ions present, this is of course much less the case (apbs2.png). You can also clearly see some of the sodium ions, which can be some distance from the protein.
My main aim is to say something about the binding of ligands in the pocket in the middle of the images.
Now, I have the following questions:
- When judging the electrostatic compatibility of ligands with the protein surface, should I consider apbs2.png (i.e. with sodium ions) or apbs1.png? (I think apbs2.png would be more fair, but it may not be ideal... see below.)
- Is there any way that I can do some kind of 'general' neutralization of a system, i.e. not dependent on the specific positions of the sodium ions from my simulation? If so, what would be a good approach to do this? (I can imagine one could adjust the electrostatic potential values, but how?)
- Would the electrostatic potential of such a 'general neutralized' system be more 'reliable' than a single structure with sodium ions from MD?
Any other comments on this are greatly appreciated. Have others looked at something similar before?