Fe-S clusters

Biological Fe-S clusters come in many sizes and flavours:

2Fe-2S clusters ligated by four cysteines

2Fe-2S clusters ligated by three cysteines and one aspartate

2Fe-2S clusters ligated by cysteines and histidines (the so-called Rieske clusters)

3Fe-4S clusters ligated by three cysteines

4Fe-4S clusters ligated by four cysteines

4Fe-4S clusters ligated by three cysteines and one aspartate

the hideously complex cluster present in hybrid cluster protein (also known as fuscoredoxin or "prismane protein")

the P-cluster in nitrogenase

etc., etc., etc.
The large number of electrons in Fe and the complexity of the possible couplings between spin states make the theoretical analysis of the electronic structures in Fe-S clusters quite difficult.
Takano et al. have recently published a paper on the differences between a Cys₃Asp ligated 4Fe-4S cluster and the "regular" (all Cys) 4Fe-4S cluster. The authors nicely analyze the influence of the Asp (and other) ligands on the electronic structure of the 4Fe-4S cluster, observe a -0.10 V difference in redox potential (vs. normal 4Fe-4S) in high dielectric constants, and offer this observation as the reason for the low potential of this cluster.
I do not accept this last conclusion for two reasons:

redox potentials of Cys-ligated 4Fe-4S clusters may differ by >0.4 V from each other, which shows that the influence of the charge distribution of the protein is much more important than the small difference observed by the authors

the 0.1 V difference found amounts to ca. 2.3 kcal/mol, which is well within the error range of the computational methods used.

Energy metabolism in brain

It is a well-known "fact" that under normal conditions glucose is responsible for providing almost all the energy needed by the healthy brain. However, it is not at all clear why that should be so: after all, fatty acids are well known to cross the brain-blood barrier. Why souldn't they be substrates for beta-oxidation in neurons? After browsing the literature, I still do not have an answer for that question. The Gene Expression Database reports that the enzymes involved in beta-oxidation are indded expressed in brain, but it is not clear if the data are from tissue homogeneates ot form purified neurons/astrocytes, etc. Back in 1993, Ebert et al.  showed that ca. 20% of the brain's energy needs may be met by medium-chain fatty acids. Drawing on earlier research by other authors, Ebert et al. concluded that astrocytes probably account for the fatty acids oxidation, while the neurons survive on glucose alone (or a mixture of glucose and lactate provided by the astrocytes themselves).

I would still like to find out any explanation for the neurons' dependence on glucose (or glucose/lactate).. Any ideas?

Should we suspect any shameless self-promotion in some Impact Factors?

Selecting the journal for your next submission is a decision with lots of variables:

how likely is the journal to find your work "sexy" enough?

what is its impact factor?

how long does the journal take from acceptance to online/paper publication?

how desperate are you to get your paper published?




Ideally, impact factor would be an objective measurement... We all know, however, that the actual relationship between "real journal impact" and the impact factor is not always perfect: a single paper with many citations in a small journal may increase its IF dramatically, even if all other papers in that journal are less cited than the papers form preceding years; citations may be inflated artificially by the authors self-citing themselves to exhaustion, bad papers may be highly cited (e.g. in refutations), etc.
I have now found (entirely by accident) a journal that increased its impact factor five-fold from 2009 to 2010. That would be surprising in itself. But the real surprise is that in August 2010, this journal published a paper that has thus far received 37 citations, ALL IN THIS SAME JOURNAL.

You may check for yourselves in Web of Science.. The paper is

Aman MJ , Karauzum H , Bowden MG , Nguyen TL (2010) "Structural Model of the Pre-pore Ring-like Structure of Panton-Valentine Leukocidin: Providing Dimensionality to Biophysical and Mutational Data" J. Biomol. Struct. Dyn., 28, 1-12



This is not the only surprise. Other papers with high citations are:

Tao Y , Rao ZH , Liu SQ (2010) "Insight Derived from Molecular Dynamics Simulation into Substrate-Induced Changes in Protein Motions of Proteinase K" J. Biomol. Struct. Dyn., 28, 143-157 (36 citations, of which 35 in J. Biomol. Struct. Dyn.)


Sklenovsky P, Otyepka M (2010) "In Silico Structural and Functional Analysis of Fragments of the Ankyrin Repeat Protein P18(INK4c)" J. Biomol. Struct. Dyn., 27, 521-539 (36 citations, of which 35 in J. Biomol. Struct. Dyn.)


Zhang JP (2009) "Studies on the Structural Stability of Rabbit Prion Probed by Molecular Dynamics Simulations" J. Biomol. Struct. Dyn., 27, 159-162 (36 citations, of which 31 in J. Biomol. Struct. Dyn. and 4 others are self-citations by the author)

Chen CYC, Chen YF, Wu CH, Tsai (2008) "What is the effective component in suanzaoren decoction for curing insomnia? Discovery by virtual screening and molecular dynamic simulation " J. Biomol. Struct. Dyn., 26, 57-64 (35 citations, of which 21 in J. Biomol. Struct. Dyn. and 11 others are self-citations by the author)

Mittal A, Jayaram B, Shenoy S, Bawa TS (2010) "A Stoichiometry Driven Universal Spatial Organization of Backbones of Folded Proteins: Are there Chargaff's Rules for Protein Folding?" J. Biomol. Struct. Dyn., 28, 133-142 (34 citations, of which 33 in J. Biomol. Struct. Dyn.)

"We are pleased to invite you....."

The recent trend toward open access science publishing has yielded a very uneven crop of journals. We do have a few respected Open Access-only publications with high quality research (PLoS ONE and many titles on BioMedCentral) but there is also a very large number of publishing firms that email researchers to solicit submissions to brand new Open Access journals. I have received several of these emails, which always claim to have selected me because of my expertise on the topic even though I have often not published anything on it, or even on related subjects. So far, I have received requests to submit reviews to:

a special issue on protein biogenesis in "Archaea". (I have studied enzymes of P. furiosus, but never did any on protein biogenesis or post-translational modifications)

International Journal of Medicinal Chemistry

Recent Patents on DNA and Gene Sequences (I have never done any sequencing, but that did not prevent the editors from considering me an expert on the area ;-)

This morning I received the most ludicrous example of "scientific" spam: I was invited to present my work on "A tale of two acids: when arginine is a more appropriate acid than H₃O⁺" to the "EPS Montreal International Renewable Energy Forum 2011". Definitely off-topic!

Computing redox potentials

First-principles computations of redox potentials in solution is a difficult task due to the large number of solvent molecules that must be included. As the computational cost increases steeply with the number of basis functions, a common approach consists of performing a geometry optimization of the reduced and oxidized species in vacuo, and then computing the energy of these species with a larger basis set and a continuum method that represents the influence of the solvent on the solute electron distribution. Besides the error introduced by assuming that the geometry does not change upon solvation, this approach includes two main sources of errors:
a) the intrinsic error of the theoretical level used to compute the electronic energies
b) the error associated with the continuum method itself.

Whereas the first error may be rigorously quantified by comparison with experimental gas phase values and made very small with the choice of an appropriate basis set/theory level combination , most continuum methods yield less predictable errors (especially when the redox-active portion of the solute is present in a very heterogenous environment, like an enzyme active site).


Dejun Si and Hui Li have now improved the continuum solvation methods by including the possibility of assigning different dielectric constants to different parts of the solute cavity surface, thus improving the description of heterogeneous environments. These authors have also shown this approach to correctly predict the relative redox potentials of the type I copper centers (optimized in vacuo) in eleven different proteins with maximum errors < 0.1 V (provided that the systems include approximately 100 protein atoms around the Cu Center). The error can be minimized to < 0.05 V by optimizing the geometries using the newly-developed heterogenuous polarizable continuum.

This new continuum method is implemented in the latest release of GAMESS, a free and very powerful quantum chemistry package available from Mark Gordon's group, at Iowa State University.

Making the most out of a failed experiment

The scientific literature is heavily biased towards positive results, and it is therefore a matter of considerable dismay to realize that the experiments one has been doing do not work. Organic letters today has a new paper showing how to snatch victory from the jaws of (experimental) defeat. The title says it all: Unlikeliness of Pd-Free Gold(I)-Catalyzed Sonogashira Coupling Reactions. Most of us would probably sigh, bang the table, and bury these results in a dissertation footnote where they might never be found by anyone. Congratulations to the authors for their perseverance and for teaching us something more about what does not work in Sonogashira couplings!