Chimera Coulombic Coloring vs. Published ESP Figures (May 2009)

Published figures of molecular surfaces colored by electrostatic potential (ESP) are usually based on Poisson-Boltzmann calculations. Coulomb's law calculations are simpler and more approximate, and do not account for the spatial distribution of high and low dielectrics, i.e., the shape of the protein.

Thus, quantitative agreement is not expected; the equations are simply different. However, such published figures are generally intended for qualitative interpretation (e.g., the positive patch binds DNA). I wanted to see whether the Coulombic Surface Coloring tool in Chimera could just as well be used for such illustrations. For this informal comparison, I chose a few published images for which the corresponding structures were available. These examples were not chosen scientifically, but they were not cherry-picked. They were all the cases I tried.

Conclusion: At least for this small sample, Chimera's Coulombic Surface Coloring tool produces results remarkably similar to the published images (more than I had expected). The default Coulombic parameters (ε = 4r, thresholds ± 10 kcal/mol·e, etc.) tend to give the best results. If the goal is to make the coloring look the same as in the published image, it can generally be achieved by changing the thresholds by a factor of ≤3 from the defaults. In my opinion, however, some of the published figures use thresholds that are too low, losing the dynamic range of the coloring.

Below are figures from Chimera only! Click the links to see the published figures.

(requires online access to the publications, such as an institutional subscription)

Structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4665-70.

See Fig 4. Figures uncredited but look like Pymol. Legend only says negative is red, positive blue, neutral white. Main point: in the complex on the right, the peptide Cterm (yellow, right end) occupies a hydrophobic cleft that is not present in the complex on the left.

Coulombic Surface Coloring defaults: ε = 4r, thresholds ± 10 kcal/mol·e. Structures 3eqs and 3eqy, altlocs B deleted, glossy lighting. [session]

Same except thresholds ± 5.93 kcal/mol·e (=10 kT/e). Note: identical results can be obtained by decreasing the Coulombic dielectric instead of the thresholds, another reason to not become overly focused on quantities.

Small molecule-induced allosteric activation of the Vibrio cholerae RTX Cysteine Protease Domain. Science. 2008 Oct 10;322(5899):265-8.

See Fig 2. Supplementary information says Pymol, APBS, ± 5 kT/e, chain B. Main point: there is a highly positive pocket for binding this extremely negatively charged ligand, inositol hexakisphosphate.

Coulombic Surface Coloring defaults. Structure 3eeb, chain A deleted, depth cuing off. [session]

Same except thresholds ± 2.965 kcal/mol·e (=5 kT/e)

A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science. 2005 Jun 3;308(5727):1480-3.

See Fig 3A (bottom view). Legend says ± 5 kT/e. Supplementary information also mentions Pymol and GRASP. Main point: this largely negatively charged protein mimics DNA.

Coulombic Surface Coloring defaults. Structure 2bm5, the highest-resolution of the several associated with this work. [session]

Same except thresholds ± 2.965 kcal/mol·e (=5 kT/e)

Crystal structure of the breakage-reunion domain of DNA gyrase. Nature. 1997 Aug 28;388(6645):903-6.

See Fig 3A (top view). Description mentions GRASP, negative red, positive blue, but not threshold values. (However, the same molecule is also shown in the previous example with thresholds ± 5kT/e.) Main point: large positive patches line the DNA-binding notch.

Coulombic Surface Coloring defaults. Structure 1ab4, dimer generated with sym and merged into one model with combine. [session]

Same except thresholds ± 5.93 kcal/mol·e (=10 kT/e)

Same except thresholds ± 2.965 kcal/mol·e (=5 kT/e)

Solution structure of the C-terminal nucleoprotein-RNA binding domain of the vesicular stomatitis virus phosphoprotein. Nature. 1997 Aug 28;388(6645):903-6.

See Fig 7c. Description mentions DelPhi, thresholds ± 12 kT [sic]. Figure made with Pymol except 7b, which is from Chimera. Main point: many of the conserved residues important in binding are charged.

Coulombic Surface Coloring defaults. Structure 2k47, hydrogens and all models except first deleted. The shape is somewhat different, but I couldn't identify which structure of the ensemble was shown in Fig 7. [session]

Same except thresholds ± 7.116 kcal/mol·e (=12 kT/e)

Another (March 2014)

Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system. Science. 2014 Feb 21;343(6173):881-5.

See Fig 2a. Description says thresholds ± 5 kT [sic]. Main point: central region is a hydrophobic protrusion for membrane interaction.

Coulombic Surface Coloring defaults. Interactive shadows. Structure 4o6d, residues named UNK deleted, which also seems to have been done for the figure. [session]