Hello scientists, I have some data and questions.
So I'm interested in calculating the interaction energies of the R group of Tryptophan (Indole) with negatively charged residues Aspartate and Glutamate. In fact, I already calculated the interaction energy of this reaction with a sample of N = 462 protein data bank files of conditions in which my principle investigator noticed that the R groups of Aspartate's or Glutamate's carboxyl oxygen atoms labeled OE2 or OD2 approached the CH2 atom Indole. (The hydrogen atom labeled CH2 on Tryptophan is on the 6 membered ring.)
The 462 PDB files contain contain molecules A with B, where A is indole and B is either the R groups of Aspartate or Glutamate, but not both. I cut the files with molecules A and B into a file A and a file B, so I could calculate the energy of both molecules minus the energy of each of the individual molecules. All energy were calculated the same way at pH 7 in a vacuum. (I think that's important to note). So now I would describe my energy calculation as ...
A + B ---> (A ∪ B),
where A = Indole, B = Either the R group of Asparatate or Glutamate,
and "∪" = union. I decided to use the union symbol because the residues of A and B have some potential energy of interaction, but no covalent bond.
I calculated the energy (E) of the products minus that of the reactants.
Energy of Reaction (kcal / mole) = [E(A ∪ B) - E(A) - E(B)]
= [-3.31 ± 2.16](kcal / mole),
Therefore the range of the Energy of the Reaction is this:
{-5.47 to -1.15}(kcal / mole)
The negative energy clearly indicates that the Energy of the Reaction is favorable or that energy is released in the reaction, and that E(A ∪ B) is more less than zero than E(A) or E(B),
where the mean energy of the reaction is -3.31 kcal/mole,
where the median energy of reaction is -3.34 kcal / mole,
and the standard deviation of the energy of reaction is 2.16 kcal/mole,
where the maximum energy of reaction is 8.225147 kcal/mole,
where the minimum energy of reaction is -9.741907 kcal/mole,
and 93.506% of the 462 reaction energies were less than 0 kcal/mole.
In all N = 462 cases of Files A, B, and (A ∪ B),
the charge of A (Indole) = 0,
the charge of B (R groups of Aspartate or Glutamate) = -1,
the charge of both molecules together or (A ∪ B) = -1
I'm considering this an anion-pi interaction in which the negatively charged residues of aspartate or glutamate's R oxygen atoms approach a hydrogen atom on the 6 carbon membered indole ring. I hypothesize that the energy of the the association should be somewhere between that of a hydrogen bond and that of an electrostatic interaction as the negatively charged residue approaches the neutrally charged indole delocalizing the electrons in the ring and creating a partial positive charge on indole's rings which encourages the association. Anion pi interactions have been observed in negatively charged ions interacting with aqueous proteins at the tryophan ring. . But I'm not sure how strong they should be in a vacuum.
I used Gaussian 09 to perform the calculations with the Ab initio method: b3lyp/6-31g(d)
What I want to know if my energy of the reaction is reasonable, and if you saw an energy of this magnitude what would you think?
Energy of Reaction (kcal / mole) = [E(A ∪ B) - E(A) - E(B)]
= [-3.31 ± 2.16](kcal / mole)
I think these energy ranges are reasonable for comparison:
Hydrogen Bonds: 1–3 kcal/mole
Electrostatic Interaction: 1.4 kcal mol-1 + (? standard deviations)
Source: https://www.ncbi.nlm.nih.gov/books/NBK22567/
I think those should probably be reported negatively. Maybe it's a matter of perspective?
I'll give you an image of the files that I'm considering. This one has Indole with the R group of Glutamate, and I'll also give you a histogram (with 60 breaks) of the energy distribution in kcal/mole.
Thanks! Again, I would like to know if my energies appear reasonable to you, and I would appreciate any help interpreting this information, or deciding if I should try a new method. (I don't know if I should call this a reaction. Association might be a proper term, but I have all the numbers.)
The energies look reasonable, but that's the only good news. B3LYP is known to very porrly describe dispersion interactions and other non-covalent interactions with errors on benchmarks sets in the 4-5 kcal/mol range. I would recomend switching to at least B3LYP-D3 or better M06-2X and calculating counterpoise correction to get meaningful results, since now they're neither reliable not publishable.
Also some papers worth reading: http://pubs.acs.org/doi/abs/10.1021/ja310834w, http://pubs.rsc.org/en/content/articlelanding/2016/sc/c5sc01386k#!divAbstract and definitely http://pubs.acs.org/doi/abs/10.1021/jp1010549
- Badges
- Science topic
- Similar topics
- Chemistry