Sunday, June 30, 2013

J. Hachmann, C. Román-Salgado, K. Trepte, A. Gold-Parker, M.A. Blood-Forsythe, L.R. Seress, R. Olivares-Amaya, A. Aspuru-Guzik, The Harvard Clean Energy Project Database
Contributed by +Jan Jensen

The Harvard Clean Energy project, lead by CCH editor Alán Aspuru-Guzik, has released the results of 150,000,000 DFT calculations on 2,300,000 compounds under the CC-BY license at The details of the calculations has been described in a 2011 Journal of Physical Chemistry Letters paper and will be described further in an upcoming paper.

The compounds in the database were selected as potential candidates for organic photovoltaics and the database contains HOMO and LUMO orbitals energies, and their difference, computed using various DFT functionals, which, in turn are used to estimate power conversion efficiency, the open circuit voltage, and the short-circuit current density using the standard Scharber model.

The HOMO and LUMO energies and gaps represent averages of several DFT methods and conformations and are calibrated against experimental data.  Details of this calibration are not given the 2011 JCP Letters paper, so they may appear in the forthcoming paper.

According to the website, will soon be augmented by a designer module that "will allow you to help us design new materials. By following simple chemical rules and using our predictive model, you can help us develop new candidates for solar cell materials."

The calculations were made possible by using the World Community Grid managed by IBM.

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

Friday, June 28, 2013

Three interesting recent Angew. Chem. papers

Contributed by Steven Bachrach.
Reposted from Computational Organic Chemistry with permission

A note here on a few recent Angew. Chem. articles of interest to readers of this blog. The first is a comment by Frenking1 concerning the “trilogue” by Shaik, Hoffmann and Rzepa2 which discusses the nature of C2, especially the notion that this molecules may possess a quadruple bond (see this post for a previous post on this article.) Frenking argues that the force constant associated with the C-C stretch in C2 is smaller than that in acetylene, so how can one argue that there is some quadruple bond character in C2? A reply from the original authors3 accompanies the comment by Frenking, and they respond by noting that the PES for bond stretching is unusually flat. I had the generally sense, though, that the authors of both articles were really talking past each other and that an opportunity for a more fruitful discussion has been missed.

The other article of note is an excellent review of de novo enzyme design as performed by the Baker and Houk labs.4 This review, authored by leaders of this effort, highlights their approach to this “holy grail” problem. The general notion is to use standard tools of computational chemistry to design a theozyme. Next, this theozyme is placed into known protein motifs with the attempt to have it fit without too much steric clash. The protein is then mutated one residue at a time to optimize the fit and binding of the theozyme to substrate. Lastly, the best targets are synthesized and tested. (The reader can see my post one of their projects: synthetic Diels-Alderase.)


(1) Frenking, G.; Hermann, M. "Critical Comments on “One Molecule, Two Atoms, Three
Views, Four Bonds?”," Angew. Chem. Int. Ed. 201352, 5922-5925. DOI: 10.1002/anie.201301485.

(2) Shaik, S.; Rzepa, H. S.; Hoffmann, R. "One Molecule, Two Atoms, Three Views, Four
Bonds?," Angew. Chem. Int. Ed. 201352, 3020-3033, DOI: 10.1002/anie.201208206.

(3) Danovich, D.; Shaik, S.; Rzepa, H. S.; Hoffmann, R. "A Response to the Critical Comments on “One Molecule, Two Atoms, Three Views, Four Bonds?”," Angew. Chem. Int. Ed. 201352, 5926-5928, DOI:10.1002/anie.201302350.

(4) Kiss, G.; Çelebi-Ölçüm, N.; Moretti, R.; Baker, D.; Houk, K. N. "Computational Enzyme Design," Angew. Chem. Int. Ed. 201352, 5700-5725, DOI: 10.1002/anie.201204077.

Thursday, June 13, 2013

Unraveling the Enigmatic Mechanism of L‐Asparaginase II with QM/ QM Calculations

Diana S. Gesto, Nuno M. F. S. A. Cerqueira, Pedro A. Fernandes, and Maria J. Ramos J. Am. Chem. Soc. 2013, 135, 7146
Contributed by Jonathan Goodman

This paper discusses the hydrolysis of asparagine

The transformation is simple, but the catalyst, L-Asparaginase II, is not. The active site of the enzyme contains a number of functional groups which work together to hydrolyse the enzyme. 

The currently accepted mechanism is that the process is related to that of a serine protease, with Thr12 attacking the amide to form an ester that is then hydrolysed. This mechanism looks reasonable. The three-dimensional structure shows that Thr12 is poised over the carbonyl of the amide, close to the π* orbital of the carbonyl and in about the right position to attack. However, studies of mutants of the enzyme do not provide unambiguous support for this proposal. 

This paper reports a computational study of the system using an ONIOM approach, with B3LYP/6-31G(d) for the high-level layer and AM1 for the low-level layer. This split approach made it possible to follow the reaction pathways for the system. Minima and transition states were recalculated using single point calculations at the M06-2X/6-311++G(2d,2p) level. This method showed that the currently accepted mechanism, summarized in the figure below showing the key Thr12-substrate interaction in cyan, was a high energy pathway, and an alternative mechanism involving the attack of a water molecule and stabilization of the intermediate oxyanion by Thr12 was more accessible. The new mechanism is surprising in that Thr12 is above the carbonyl group and so not in a good position to interact with the lone pair of the amide carbonyl. However, this configuration does fit the grand jeté orientation that we recently highlighted for mechanisms involving oxyanion holes (doi: 10.1039/C2OB06717J).

This paper demonstrates that the calculations can provide a sufficiently accurate analysis of the system to inspire an alternative to the currently accepted mechanism. The new mechanism fits all of the available experimental data; it was hard to see how some of the experimental data fitted the original mechanism. The new mechanism, therefore, is to be preferred. If both mechanisms had fitted the available experimental data, would these demanding calculations have been enough to change the currently accepted mechanism to the new process?