Thursday, July 14, 2011

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.
  • Monday, July 11, 2011

    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?

    Wednesday, July 6, 2011

    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.)