Tuesday, November 6, 2018

In praise of "Arabian Journal of Chemistry"

In early October 2017 I submitted a  paper to Royal Society Open Science (RSOS). It took more than four months before I got any update on its status. After conflicting reviews, RSOS contacted an additional reviewer, who took TWO months to write a two line "report" which rejected my paper due to "lack of novelty" in spite of no other study of the subject matter existing in the literature. I decided then to eschew RSOS for ever and looked for another Open Access journal for my submission. 
Since I currently have no funding, absence of author processing charges was an important consideration. I found out about the "Arabian Journal of Chemistry" and looked into it: in spite of its obscurity, they have a decent Impact Factor (which shows that their papers are at least read within the community and solid enough to warrant being cited) and their APCs are borne by the King Saud University. I sent them my paper, which was unfortunately rejected although the reviewer reports were more consistent with a "Major Revisions" decision. The peer-review process, though, was exemplary: in less than two-and-a-half months, they provided me with SIX solid peer-review reports with enough actionable insights that I could incorporate into my paper to eventually get it published in J. Phys. Chem. A.
 I can only commend them for the utter professionalism, speed and quality of the whole process. I wish Arabian Journal of Chemistry all the best, and that its high standards and level of review will soon make it known among chemists as a premium journal. They  sure deserve that!

Saturday, October 27, 2018

A warning to readers of "Computational studies on the regioselectivity of metal-catalyzed synthesis of 1,2,3 triazoles via click reaction: a review" published in J.Mol.Model. (2015) 21,264-291



J. Mol. Model. instructions for authors clearly state, in the section on “Ethical responsibilities of authors” that “Proper acknowledgements to other works must be given (this includes material that is closely copied (near verbatim), summarized and/or paraphrased), quotation marks are used for verbatim copying of material, and permissions are secured for material that is copyrighted”. Unfortunately, the paper "Computational studies on the regioselectivity of metal-catalyzed synthesis of 1,2,3 triazoles via click reaction: a review" , authored by Tayebeh Hosseinnejad, Bahareh Fattah and Majid M. Heravi contains abundant citation deficiencies and apparent breaches of this policy.  To ensure that readers do not misunderstand the origin of some data reviewed in that manuscript and that proper credit is assigned to the original authors, I provide a (possibly incomplete) listing of those:
- a long section (p.278-282) describes  the computations of the reaction mechanism of the Cu-catalyzed addition of azides to 1-iodoalkynes (performed by Lal, Rzepa et al. [1] and published in ACS Catalysis (2014) 4, 2274-2287) without a reference to the original paper . These results are introduced in p.278, 2nd column , 3rd paragraph, line3,  with the text “The calculated result showed by using [CuI(PPh3)3] as the catalyst…” and finish in p.282 (1st column, 2nd line) : “Very similar results have been obtained by using [CuCl(IPr)]”. The lack of citation leads the reader to mistake this whole section for original research by the review’s authors. This perception is reinforced by the lack of attribution of the results of schemes 15-18 to Lam et al.: these schemes are virtually identical to schemes 8, 10, 11 and 12 of the original publication, and should have been captioned by the review’s authors as “adapted from Lal et al.". The only citation in the captions to these schemes refers, instead, to the paper describing the def2-SVP basis set.
- In p.274, second column, first paragraph, the description of the computational study of reaction of a sugar azide with (E)-trifluoromethyl-2-tosylethene[2] consists of a long, detailed paragraph, beginning with “Single-point energy calculations were performed at the M06-L/6-311+G** level of theory (ref. 114) with PCM method in toluene employing the M06-L/6-31+G* optimized geometries.” Ref. 114 refers to Hehre, Radom, Schleyer and Pople’s “Ab initio molecular orbital theory” (incidentally wrong as a reference to either M06-L or the 6-311+G** basis set) and since no other reference is provided it is likely that, as in the first example above, readers will think that this paragraph refers to original work by the review’s authors. Only in the end of the paragraph does the reader find a reference to the original work (their ref. 109) although in a somewhat opaque form, which does not clarify whether the citation refers to a specific finding or to the whole paragraph: “Strictly speaking, M06-L/6-311+G** and M06-L/6-31+G* calculations proposed that TS of 1,5-DTs is energetically preferred by 0.4 kcal mol1 compared to the corresponding 1,4-DTs (Fig. 7), which is in agreement with the experimental result (ref. 115), and the calculated free energy of activation ΔG‡  also predicts that the formation of 1,5-DTs is preferred by 2.48 kcal·mol-1 compared to the corresponding  1, 4-DTs (ref. 109)”. Figures 6-7 in this review are barely reworked un-attributed versions of Figs. 1-2 of ref. 109, with the energies changed from kJ/mol to kcal/mol.

- Figures 1-4 of this review are, likewise, lightly re-worked versions of figures under copyright with other journals[3] (See Figures 5, 9 10 and 11 of J Org Chem (2012) 77, 75-89), and should be marked as “adapted from Gold et al. (2012)” . Figure 8 is an unattributed lightly re-worked version of Fig. 4 from their ref. 116 (Kumar et al. (2010)[4] ), and table 1 is taken verbatim (again without attribution) from table 2, ref. 116.  Figures 15 and 17 differ from figures 1 and 3 in Luo et al. J. Org. Chem , 79, 11970-11980 [5]  (ref. 169 in the review) only in the coloring of the azide and alkyne moieties, again without attribution or (presumably) permission from the publisher. Figures  16, 19, and 20 are cropped versions of figures 2, 5 and 6 in [5]. Figure 18 in this review is a duplicate of figure 17. Fig. 21 is an unacknowledged adaptation of fig. 7 in [5]
- In page 277, the reference cited  in “The reactants, products, and transition states were optimized at B3LYP/6-31G* level of theory (ref. 123)” refers to an MP2/6-31G*//HF/6-31G* study of an unrelated reaction.
- In page 278, the reference provided to “the optimized electronic structure was obtained by solving the Kohn-Sham equations self-consistently (ref. 141)” is not related to the Kohn-Sham equations, the self-consistency procedure, the algorithm, or software package used, but to the paper describing the def-2 basis sets.
- Scheme 20 describes to an iridium-catalyzed reaction, but its caption refers instead to a ruthenium-catalyzed one.
- Fig. 12 is an unattributed copy of Fig.4 in [6]. This figure is referred in p. 284, second column, and the original citation (ref. 167 in the review) is not mentioned until p. 286.  Fig.14 and  Schemes 21, 22, and 23 are unattributed copies/reworkings of Fig. 5 and Schemes 2, 3, and 4, respectively, in [6]. Table 2 (p. 288) is an unattributed copy of Table 1 in [6].
- in p. 290, second column, the results of computational research on the iridium-catalyzed azide-alkyne coupling are introduced as “Origins of the observed regioselectivity have been studied mechanistically by performing quantum chemistry calculations on the role of the catalyst in reaction mechanism (illustrated in Scheme 25). All molecular structures and energies were calculated at M06 level of DFT method (ref. 82). The effective core potentials (ECPs) of Hay and Wadt with double-ζ valence basis sets (LANL2DZ) (ref. 170) were used for Ir and 6-31G(d) basis set was employed for N, S, Cl, Br, and O as well as the C atoms in the triple bonds of alkynes and double bonds of 1,5- cyclooctadiene (cod) and 6-31G basis set was used for all other atoms.”  The reader has to wait for a reference at the end of the page to learn that the results discussed originate from Luo et al. [5] (ref. 169 in the original).
-in p. 293, the review’s authors state “The calculated energy profiles for the mentioned possible oxidative couplings have been presented in Fig. 16 and the free energy barriers for ligand dissociation/association processes (e.g.,A to B1 and A to B2 in Fig. 16a, b) were obtained through the method proposed by Hall and co-workers (refs. 171, 172) (Fig. 17)”, without mentioning that those computations were performed by Luo et al.[5].

I understand that the labor-saving reuse of previous images enables authors of literature reviews to more fully devote their minds to the important job of making sense of a wide literature instead of futilely re-inventing the wheel. As such, I do not think that authors of a review paper necessarily have a special obligation to re-draw the computed geometries of intermediates and transition states in every image (e.g. using a different molecular viewer or a different viewing angle), or the potential energy surfaces of every mechanism, even though generating such images anew is nowadays very straightforward due to the commendable practice, widely embraced by the computational chemistry community, of providing at least the geometric coordinates in readily-usable formats. Authors should, however, ensure that readers are not unwittingly misled regarding the provenance or authorship of any of the data they show, and that their presentation does not lead future workers to fail to cite the original reports. An exemplary use of proper citation practices in reviews can be found, e.g.,  in Johansson et al.’s recent overview of ruthenium-catalyzed azide alkyne cycloaddition reaction[7], where every scheme is clearly attributed to the original proponents and the supporting information accompanying computational papers is used to generate new views of the relevant molecules.



1.        Lal S, Rzepa HS, Díez-González S (2014) Catalytic and Computational Studies of N-Heterocyclic Carbene or Phosphine-Containing Copper(I) Complexes for the Synthesis of 5-Iodo-1,2,3-Triazoles. ACS Catal 4:2274–2287. doi: 10.1021/cs500326e
2.        Sahu D, Dey S, Pathak T, Ganguly B (2014) Regioselectivity of Vinyl Sulfone Based 1,3-Dipolar Cycloaddition Reactions with Sugar Azides by Computational and Experimental Studies. Org Lett 16:2100–2103. doi: 10.1021/ol500461s
3.        Gold B, Shevchenko NE, Bonus N, et al (2012) Selective transition state stabilization via hyperconjugative and conjugative assistance: stereoelectronic concept for copper-free click chemistry. J Org Chem 77:75–89. doi: 10.1021/jo201434w
4.        Kumar KK, Kumar RM, Subramanian V, Das TM (2010) Expedient synthesis of coumarin-coupled triazoles via “click chemistry” leading to the formation of coumarin–triazole–sugar hybrids. Carbohydr Res 345:2297–2304. doi: 10.1016/j.carres.2010.07.037
5.        Luo Q, Jia G, Sun J, Lin Z (2014) Theoretical studies on the regioselectivity of iridium-catalyzed 1,3-dipolar azide-alkyne cycloaddition reactions. J Org Chem 79:11970–11980. doi: 10.1021/jo5018348
6.        Boz E, Tüzün NŞ (2013) Reaction mechanism of ruthenium-catalyzed azide–alkyne cycloaddition reaction: A DFT study. J Organomet Chem 724:167–176. doi: 10.1016/j.jorganchem.2012.11.011
7.        Johansson JR, Beke-Somfai T, Said Stålsmeden A, Kann N (2016) Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications. Chem Rev 116:14726–14768. doi: 10.1021/acs.chemrev.6b00466

Wednesday, October 18, 2017

Some common-sense advice regarding responding to peer-reviewers

Editing and (especially) reviewing are mostly thankless jobs which take time and attention from the busy schedules of reviewers. Facilitating their work (or at least not making it harder than absolutely necessary) is therefore a very important way to improve the odds of a favourable decision. As such, it is absolutely crucial that every reviewer/editor comment be acknowledged and addressed. Authors may always decline to make a requested change by presenting their reasons, but failing to mention any one of the reviewer's comments (even if to reject their pertinence) may come across as evasive and less than fully transparent. Moreover, it is one of the worst things an author can do to their chances of a favourable outcome: at best, it can be taken as a passive-agressive way to signal discontent with "dreaded reviewer#3". At worst, it can be mis-interpreted as an attempt to hoodwink editors.  In any case, it increases the probability of tipping the editor's judgment away from a positive decision.


A few hints to help reviewers appreciate your response:

  • When you prepare your rebuttal,  provide the full text of all of the reviewers' comments to the initial version of this submission, interspersed with your detailed replies to each point (preferably in a different font, for ease of reading).
  • Some journals request re-submissions to be accompanied by a copy of the manuscript file with highlighted changes. In that case, do not highlight those changes manually: use your word-processor built-in "track changes feature" instead, to compare the initial submission to your modified manuscript.

Friday, July 7, 2017

Today I became dreaded reviewer #3

I am now writing a referee report. I usually frame my comments diplomatically and try to be constructive (you will have to take my word for it...). Unfortunately, my first comment to these authors is uncharacteristically harsh, and I wish I had not needed to write it:
"I do understand that productivity and impact metrics like the number of citations, h-index, etc. are wrongly used by intitutions and funding agencies to measure research productivity, and that scientists are implicitly (or explicitly) pressured to inflate them. I cannot, in good conscience, agree with that practice but would have kept silent if a manuscript cited a couple of papers by the authors in the introduction. However, in this manuscript 46 references are cited, of which 23 (number 8-11, 15-19 , 21-23 , 34-42 , 44-45) are from the current authors. None of these 23 citations refers to specific results from those papers: they are rather cited as examples of well-known facts which either require no citation or should cite seminal papers/reviews in the area. I will not accept this paper in any form, for publication in this or any other journal, if those references remain."

I am afraid such comments to authors and editords must become much more common to stop the continuous gaming of the system. As long as metrics are used for ends they were not designed to, authors will (more or less grudgingly) try to game them, if only to ensure that they do not "fall behind" in comparisons with colleagues who feel even less compunction to game. Race to the bottom, and all that...

Thursday, April 28, 2016

New scientific biographies wanted....

Biographies fulfill several different roles: they may simply satisfy one's curiosity over the lives/achievements of the biographees, provide tasty morsels of gossip or interesting stories, or play an "educational" role. Traditionally, the "educational role" of biographies has focused on their presentation of "role models" - whether moral, political or social - or the conditions/life experiences which led to the special significance of the biographee. Scientific biographies follow the same pattern. Like traditional biographies, they are usually limited to people of special significance: trailblazers, mavericks, geniuses, and people who left a mark on their scientific discipline or on the public perception of the worth of their subject.

I wish there were also another kind of biography, devoted to the intelectual careers of "normal" researchers: people who simply follow their intelectual curiosity, who are constrained by the amount of funding they can get and who pass away in obscurity after adding their small contributions to our colective knowledge. I do not want "human interest stories" played by researchers: I rather long for a description of their intelectual journeys, why they decided to study a specific problem, what kinds of mental connections they made (and why), in what measure their interpretation of their results was "commonplace" or (in contrast) specifically triggered by insights coming from seemingly unrelated work they had performed earlier, etc.

I want to read stories that show how each of these normal people, in their own way, made work which seems ordinary but is, in contrast, highly personal: work that would not have been done, or which would not have yielded the same insights, if that scientific question had been tackled by someone with a different research history. I am reasonably confident that most rank-and-file scientists would be fitting subjects for this style of biography, and that the study of these stories would teach us a lot about the roles that creativity, personality, luck and culture play in the fostering of a thriving research environment. 

Friday, December 11, 2015

On the difficulty of finding peer-reviewers

I have recently become an Associate Editor at PeerJ. I had several motivations for this:
  • I strongly believe in their mission, and am very happy with my three publishing experiences with them.
  • I mostly work alone and therefore my papers, in the long run, will not be a profitable for them. I felt that I should give them some extra support in exchange for their extremely low number-of-authors-based APC.
  • As a mid-career researcher at a little-known teaching-based institution, I reasoned that this opportunity might increase my visibility and improve my CV.

I am enjoying my run as an editor. So far, I have shepherded seven papers through the publishing process: one of them was published a week ago, I rejected one "on arrival",  and five of them are undergoing review.  I target my peer-review invitations to people who have recently published work using the same methods, or studied the same question, both for the obvious expertise and hoping that they will find the paper interesting. Still, I was quite surprised with how hard it is to get people to accept reviewing papers: for two papers, I managed to get two reviewers with around 6-8 invitations, but my latest assignments required more than 15 invitations each!  I understand that everybody is busy researching, writing papers, applying for funding, etc., but I never thought that the acceptance rate for peer-review requests would be < 15%. I do not get many peer-review request myself, but I do believe I have an obligation of accepting as many requests as possible (and reviewing them promptly), and I thought this was the "common" mindset... Maybe the people I target for my invitations are simply too senior and are therefore swamped with review requests, but the emails of "non-senior" members of a Lab are too often hard to find, due to the common practice of including only the the lab leader "corresponding author".

Any thoughts/suggestions/gripes?



Wednesday, July 8, 2015

Gamess (US) frequently asked questions. Part 7: How to distinguish alpha from beta orbitals in the $VEC deck

Each line in a $VEC group contains the coefficients of five basis functions for a given orbital. These are formatted in a special way, with seven numbers in each line. These numbers are:

1st) the number of the orbital to which the coefficients belong (written with at most two characters, so that 1 means orbital 1, .. , 99 means orbital 99, 00 means orbital 100) . This number is repeated in the beginning of every line, until all coefficients for that orbital have been written

2nd) this number tells the program how to assign the coefficients to the basis functions. "1" means that the coefficients are for basis functions 1-5, "2" means that the coefficients are for basis functions 5-10, etc. In general , that number "n" directs the program to assign the five coefficients present in the line to basis functions 5*(n-1)+1 to 5*n.

3rd to 7th) coefficients of five basis functions

BETA orbitals are punched as a group immediately after all ALPHA orbitals.

This format entails that in molecules with more than 100 orbitals the $VEC group contains several blocks with the same 1st number. For example, in a molecule with 200 orbitals, alpha orbital 27 is described by the first block of lines beginning with "27", and alpha orbital 127 is described by the SECOND block of lines beginning with "27".

I usually find the beginning of the BETA orbitals by repeating a search for the string " 1 1" : if that string is preceded by a block beginning with "00 1", it usually refers to orbitals 101, or 201, etc. (the exception being those systems with exactly 100, 200, etc. orbitals). If string " 1 1" is NOT preceded by a block beginning with "00 1", you are sure to have found the beginnning of the BETA orbitals

Tuesday, April 28, 2015

How does OA benefit my research?

Jan Jensen has written an interesting post describing how his decision to publish only on Open Access outlets has influenced the way he tackles research questions.  One of the benefits he points out is that choosing to publish in a journal which performs a "scientific soundness-only peer-review" instead of a "sexyness/interest and scientific soundness peer review" allows him to focus on "truly challenging and long-term research questions without worrying whether or where I will be able to publish".  I think that option already existed before OA and the advent of the mega-journals: we simply had to decide to be satisfied with publishing on IJQC or Theochem whenever the Editors of JPC, JCP, JACS, Angewandte et al.  pronounced our research "too specialized and not of enough interest to our broad readership", and to accept the derision of peers who look down on papers published on those and other low-impact journals. (I admit I am often guilty of this).
To me, the true advantage does not lie on OA itself, but on the open review model (used e.g. by PeerJ), which allows authors to publish the reviews at the same time as the paper. I feel this functions as a much stronger "validation" of the quality of the work, as readers immediately have access to a truly independent measure of the strengths and weaknesses of the manuscript.
How does OA benefit my research? I am not sure it benefits my research methodology and/or choice of research questions since, as one of only two computational chemists at a small teaching-driven University, I  have long decided to research whatever obscure subtopics catch my fancy due to obvious lack of resources to compete against larger/well-funded groups working in sexier topics/enzymes. My decision to embrace an open science model, in contrast (e.g. figshare) has benefitted me more directly by forcing me to archive my results in a more transparent way, with proper "understandable" filenames instead of idiossyncratic names chosen on the fly... That is something I should have done anyway even without the open science model, but that was the nudge which brought me to the "Light" side.

Wednesday, April 22, 2015

When the description of methods in a scientific paper becomes optional.

I have just read a paper describing some very interesting tailoring of enzyme specificity on a P450 enzyme. I was, however, surprised to find that no description of the experimental methods was present in the paper itself, but was only available as Supporting Information. Upon examination of the instructions for authors in the journal I learned that, although being online only (and therefore lacking any space constraints), this publication enforces a 40-thousand character limit on the published papers and specifically states that the experimental section is optional. Traditionally, Supporting Information includes accessory data which would be cumbersome to include in the paper.  In this journal, it functions instead as a cumbersome way to access a vital part of information which should be part of the paper. I cannot even begin to understand why any reputable publisher would, in the absence of any printing costs, force their authors to split their manuscripts and "demote" the potentially most useful portion of the paper to the Supporting Information.
That's ACS: proudly claiming to "[publish] the most compelling, important primary reports on research in chemistry and in allied fields" while making it difficult for readers to have access to that same information.

Thursday, March 19, 2015

My new preprint is up

As part of their undergraduate training, our students are required to write a short thesis. Usually, due to the paucity of research funding, their theses take the format of a literature review. A few years ago, however, I proposed a computational study to the student I had been assigned. Despite no previous acquaintace with the subject, she eagerly took the task and performed some computations on possible reaction mechanisms of the organomercurial lyase MerB. She only had the time to compute a few of the possible pathways and therefore, after she had written her thesis with the data she had managed to gather, I completed the analysis of  the other pathways we had thought of at the time, and a few that we had not envisaged. Writing it as a paper took me much longer than I had anticipated, mostly because I kept postponing it due to the thrill of running computations on other enzymes and projects. I have now managed to finish it and submitted it to PeerJ, where it is undergoing review. I have made it available as a Preprint, and would be thankful for any comments about it.


Addendum: the paper has been published

Saturday, February 7, 2015

On the wrong use of expressions such as "evolution's null hypothesis"

A new paper published in PNAS has been in the news lately, claiming to have found 2-billion-years old fossils of sulfur-metabolizing bacteria undistinguishable from modern specimens. The abstract is somewhat cautious "The marked similarity of microbial morphology, habitat, and organization of these fossil communities to their modern counterparts documents exceptionally slow (hypobradytelic) change that, if paralleled by their molecular biology, would evidence extreme evolutionary stasis." (emphasis added). In the press release and in their talks with the media, however, the authors of this study have been much more forceful and hyperbolic: they directly claim that these organisms have not changed at all! As any microbiologist worth its salt would attest, it takes a lot more than morphological similarities to establish that two microbial communities are composed of the same species. Otherwise, metabolic tests with dozens of substrates would not be needed to distinguish microbial species: we would simply need to throw the little bugs under a microscope and see what they looked like! How could the authors possibly be sure, simply from their tests, that microbial adaptation to the environment had achieved that of modern bacteria by the time their sample fossilized?

More than this extraordinary leap of logic, I was grated by the author's claim that such a lack of evolution would be in agreement with evolution's null-hypothesis of no biological change in the absence of changes in the physico-chemical environment, and it therefore strengthens the case for evolution.... How is it possible to cram so many errors and inaccuracies in such few words? How could the peer-reviewers let such inane nonsense appear in the title of the paper? Let us start to unravel the many mistakes in this formulation:

  • What the authors call "evolution's null hypothesis" has NOT (as far as  I have been able to ascertain) ever been claimed as "evolution's null hypothesis" at all: it is well-know, at least since the seminal work by Kimura, that the strongest driver of genetic variation is not the positive selection of advantageous mutations but the random fixation of neutral (or barely neutral mutations). Indeed, in humans only ca. 400 of the estimated 16500 genes show strong evidence of positive selection, even though all of the genes show variation from those of closely-related species.  It is therefore NOT at all expected that genomic stasis would be observed over a long period of time. Stating (as the authors) that observing no  change in these organisms is a confirmation of the mechanisms of evolution reveals a shocking lack of knowledge regarding  molecular evolution. And the authors have not even proved that there was no change: that would require establishing that their ATP-producing metabolism is as efficient as that of their modern counterparts, that they are able to use the same substrates, and contain all the same  enzymes, etc....
  •  By claiming that an unchanging environment leads to an immutable species, the authors commit a further logical fallacy: after all, there was a time (let's call it t0) when the ancestor to that community first entered that unchanging environment. If an unchanging environment leads to evolutionary stasis, then the authors are claiming that at time t0+1 million years the species would be equal to that at time t0, or that at t0+2 million years, and so forth. But of course adaptation to an environment is not instantaneous, unless the parent ancestor already possesses all enzymes needed to thrive there (and this is most unlikely, as there has been no selective pressure for that). An unchanging environment therefore causes evolutionary pressures, at least in regards to the first cells which venture there.
  • When an observation is compatible with different theories, it cannot be used to further any of them: after all, seeing no change in 2 billion years could also be used to argue for the immutability of species. It is therefore logically fallacious to present it as proof that Darwin was right. Also, evolutionary theory has also developed a lot since the writing of "On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life". Shouldn't other workers, like Kimura, Felsenstein, Farris and Gould be acknowledged? 
  • Why would any scientist need to claim that “the findings therefore provide further scientific proof for Darwin’s work.”? Do astrophysicists need to state “the findings therefore provide further scientific proof for heliocentrism” every time that a new comet is found, its orbit is computed, and it is found to move around the sun rather than around the earth? Do anthropologists working in the Balkans need to point out that “the findings therefore provide further scientific proof that human societies do not all resemble hunter-gatherer groups?” The curious insistence of American-based media to frame biological discoveries as a supposed debate/beauty-contest between "evolution" and "creationism/immutability of species/intelligent design" is completely mind-boggling to any European, whether religious or not. This insistence was also displayed in Neil de Grasse Tyson's "Cosmos", which, unlike Sagan's masterpiece, seemed more interested in scoring debate points against a sub-section of its domestic audience than on presenting the astounding amount of knowledge mankind has gathered in the few millenia we have spent since the dawn of agriculture.



Claims unwarranted by data, exaggeration and PR stunts: all of these are usually as ascribed (rightly or not) to politicians, polemicists, salespeople and shady companies seeking to attract capital. Do we really want science to be tarred by the same brush?

Monday, September 8, 2014

Making good on my "Open Access" pledge


My most recent paper has just been published in PeerJ . It was a LONG time in the making, to the point that my 12-yo daughter once told me (only half-in-jest), that I should "cut my losses and forget about it". I am quite happy about how it turned out: besides describing an analysis of a reaction mechanism and the influence of the redox state of a hard-to-converge Fe-S cluster , it also contains  the first computations including the weighed contributions of 1.2*1013 protonations states of a protein on the reaction it catalyzes. The computational approach described here is relatively simple to perform provided that one has a good estimate of the relative abundances of those protonation states, which can be obtained through Monte Carlo sampling  once the site-site interactions have been computed with a Poisson-Boltzmann solver. To my mind, this is clearly superior to the usual approach of considering only  the "most likely" protonation state (which may often not be the state with the most significant influence on the electrostatic field surrounding the active site). What do you think of it?


Programs needed to use this approach:
MCRP, by Baptista et al., ITQB, Lisbon
MEAD, by Don Bashford, currently at St. Jude Children's research hospital
Any molecular mechanics code, to compute the change of the total electrostatic energy as each individual amino acid is protonated/deprotonated



Tuesday, July 22, 2014

Challenges of teaching Biochemistry to Health Sciences students

Had anyone told me, 20 years ago, that I would earn my living as a lecturer, I would have considered it as a put-down. I did have a lot of respect and appreciation for (most of) my lecturers at the University of Porto, but I expected to become a full-time scientist, rather than a "lecturer who finds time to do some science in-between classes/grading" or a "researcher with required part-time lecturing duties". Real life disabused me of that expectation: due to the dearth of other scientific jobs in Portugal, I did become a "lecturer who finds time to do some science in-between classes/grading" after finishing my PhD. 

The culture shock I experienced when I first lectured to Health Science Students left me unable to speak about much more than the woes  of teaching for the best part of a year. A big portion of my surprise came from my first-contact with regular students who attended my lectures simply because they were required to by the University, rather than due to recognizing the subject as a relevant background for their (mostly) vocational training as Physical Therapists, etc. Being required to take most classes to graduate  (rather than choosing large part of the curriculum around a core subset) is a very common feature of university curricula in Portugal. In principle, it is meant to ensure that all students have a balanced curriculum and do not "flee" the hardest subjects. In practice, it also tends to lead to ever larger classes of those same "hard subjects", since students tend to consider those lectures as bureaucratic hurdles thrown at them, rather than as valuable knowledge and therefore feel disengaged, alienated and fail them in large numbers.

All classes I have taught (Biochemisty, Organic/General/Analytic Chemistry, Basic Mathematics/Statistics) fall into the "hard subjects" class. In my first years of lecturing, I had a most demotivated cohort of students. My expectations regarding their performance were generally very unrealistic, as my baseline comparison was my own student experience at my "alma mater", where I was surrounded by engaged student peers who were motivated into learning pure scientific subjects, and did not regard them as "filler" or "bureacratic hurdles" aimed at winnowing the sutdent body. Moreover, my "alma mater", the Faculty of Sciences at the University of Porto, was famous among students by its harsh grades: attrition was relatively high, less than 20% of those graduating from its Chemistry or Biochemistry curricula would have an average grade of 16/20 or 17/20, and higher final grades were virtually unheard of. In other Portuguese Universities, final average grades of 18/20 were common, even though their student body was of the same (or even slighly lower) quality, as judged by their entry grades.

I eventually adapted to the students' expectations, and developed a teaching method that engages students and apparently motivates them (as judged from the appreciative comments in teacher evaluation forms). However, I find that this only seems to work during class time: students pay attention, seem to be making all the right connections (as long as I softly nudge them towards the right path, etc.), congratulate me on the quality of lectures, etc. In tests/quizzes/exams, however, a strong disconnect appears: ca. 50% of my students still struggle with many concepts that I would consider as absolutely basic. Why does this happen?

I have just found out that there is a proper name to what is happening in my classes: pseudoteaching (defined as " The concept [...] that even the most outwardly perfect lesson can result in students not actually getting what it is you wanted them to understand."): along with this, there is also pseudolearning ("Going through the “expected” steps without extracting a solid, working understanding of a topic would") and pseudostudying (which I would define as "reading and working the material to the point where one feels tired  but without actually taking anything from the exercise due to inability to distill the core concepts into working knowledge").  I cannot prevent students from pseudolearning or pseudostudying (apart from exhorting them to rest properly, keep their blood sugar levels up while studying and work/study in short bursts daily rather than pulling all-nighters on the eve of the tests). Avoiding pseudoteaching is in my power, but I do not (yet) know how to: Jan Jensen (following Mazur) advocates a flipped classroom model where exposition occurs outside class time (using short video lectures and key exercises) followed by solving exercises "in-class" with free exchange of ideas among students (peer-instruction). I do not think this  method would help with my students, though: a previous experience of short (< 10 minutes) in-class quizzes led to class disruption, acutely stressed students during and after the quiz and minimal improvement in weekly off-class engagement with the study material. What would you suggest me do?

Thursday, July 17, 2014

Do you want to publish for free in PeerJ?

I started following the Open Access movement ca. 2 yrs ago, mostly through the blogs of Michael Eisen, Jan Jensen and Mike Taylor. I was obvioulsy well aware of the successful OA outfits, like PLOS and BiomedCentral, but had never considered publishing there due to the shortage of funds and the non-reimbursability of such expenses by my country's Science Foundation. I joined PeerJ shortly after they "opened for business", due to their their very small fees and because of commitment to transparent peer-review , which to my eyes sets them apart from the wide number of OA venues which spam email boxes daily all over the world. 
After publishing my first paper on PeerJ, I have received five referral codes from them, each of which entitles an author to the free publication of a paper in PeerJ. The codes expire on August 10th. Should you wish to take advantage of one of these, please drop me a line. PeerJ only accepts submissions on the area of Biology, which is defined very broadly (from ecology and paleontology to virology, bioinformatics and computational biochemistry).

Addendum (July, 21st, 2014): Four codes have been distributed. One left to go

Addendum (September, 14th, 2014): I have received five new codes, valid through October 2nd, 2014. Any takers?

Tuesday, June 17, 2014

Femex 2014 in Oslo has just ended

I thoroughly enjoyed the second "Promoting Female Excellence in Theoretical and Computational Chemistry" conference, both in choice of speakers and convivial atmosphere. The ratio of female/male speakers obviously favored females, but considering the nature of the conference I would not mind if it were even more skewed towards the female end of the scale, as it probably encourages audience questions from women. The format was very adequate, but ratio between established/early-career speakers might probably be adjusted slightly (for example by including a dozen more  presentations selected from poster submissions) to enable increased "name-recognition" of younger researchers.



An extra day or two, and some more free time for socialization would have been very welcome: I found that the enthusiasm and conversation flow increased substantially after the banquet talk, but by that time the meeting was coming to an end and productive conversations had to be cut short due to the need to catch the flights home. If the "after-banquet talk" could be moved to the first night of the conference, the focus of conversations during the meeting might have included more reflexion on the sociology of our profession, the way that the subtle biases which discourage hiring scientists with a publication-gap of a few years are built/accepted/torn down, and so forth. That talk did serve as a wonderful conversation starter.



I loved the presence of  children in the meeting, and think that a specific sentence in the conference website stating that they are welcome to the conferences would have a positive effect in lowering barriers to attendance, and in removing the prevalent "productivity-minded" biases which make graduate students, post-docs, non-tenured faculty feel that embracing a scientific career must lead to a neglect of other important parts of life. No matter how many "empowering" talks, positive discrimination, awareness campaings, etc., an academic culture where powerful figures of authority (whether star professors, PIs or funding agencies) demand or expect that researchers put their personal life behind their scientific productivity  skews the resulting researcher pool towards the obsessively-driven, hyper-ambitious, un-empathic tail of the population spectrum.  Whether that tail is mostly male, mostly female, or "equal-opportunity", it favors non-collegial behavior and chases good people away. Hyper-ambitious researchers may be very productive, but they cannot produce much science if their behavior leads to talented people fleeing towards other endeavors.

Congratulations to the organizing team, and a heartfelt "thank you" to all participants.

Thursday, April 24, 2014

Gamess (US) frequently asked questions part 6: Obtaining proper SCF convergence (Anti-)ferromagnetic coupled Fe-S clusters

Obtaining SCF convergence of FeS clusters is a very demanding task.
The problem in FeS clusters is the arrangement of spins on the Fe atoms: if you have a cluster with 4 Fe atoms, each of them with 5 up-spins, and a total spin of zero, the arrangement of spins on the atoms could be
  • Fe1 and Fe2  up-spin, Fe3 and Fe4 down-spin; or
  • Fe1 and Fe4  up-spin, Fe2 and Fe3 down-spin; or
  • Fe1 and Fe3  up-spin, Fe2 and Fe4 down-spin;
The problem is compounded if you have a mixture of Fe2+ and Fe3+, which may lead to 12 (or more) different spin arrangements, depending on the number of Fe2+ atoms. However, if you have a good guess SCF for one instance instance, you may simply substitute the coordinates of Fe2 with those of Fe4 to get a comparably good guess for the second instance, and so forth... This is the approach suggested by Greco, Fantucci, Ryde, de Gioia (2011) Int. J. Quantum Chem. 111, 3949-3960. Obtaining the guess for one of the instances is in itself quite difficult, and I usually follow the approach outlined by Szilagyi, R. K. and Winslow, M. A. (2006) J. Comput. Chem., 27: 1385–1397  .
It goes like this:

- obtain orbitals for bare Fe2+, Fe3+, S2-, and isolated ligands, with proper spins on the Fe atoms (5/2 for Fe3+, 2 for Fe2+)

- Manually split the "alpha/up" and "beta/down" portions of the resulting  $VEC groups. For example, assuming you have a system with three Fe atoms (two Fe2+ and one Fe3+) with total spin S=5/2 and the $VEC groups for bare Fe2+ and bare Fe3+, you should cut the $VEC groups of Fe2+ and Fe3+ as:


$VEC  for the alpha (up) electrons of Fe2+   (let's call it "Fe2+_5_d_electrons")
$VEC  for the alpha (up) electrons of Fe3+   (let's call it "Fe3+_5_d_electrons")
$VEC  for the beta (down) electrons of Fe2+   (let's call it "Fe2+_1_d_electron")
$VEC  for the beta (down) electrons of Fe3+   (let's call it "Fe3+_0_d_electrons")
The total spin S=5/2 in this sample problem implies that  both Fe2+ atoms spins should annull each other, i.e., one Fe2+ is mostly "up" and the other is mostly "down". Building the new guess for the "up" electrons should therefore include:

"Fe2+_5_d_electrons" for one of the  Fe2+ ions,
"Fe2+_1_d_electrons" for the other  Fe2+,
"Fe3+_5_d_electrons" for the Fe3+

Building the new guess for the "down" electrons should  include:
"Fe2+_1_d_electrons" for the FIRST Fe2+ ions,
"Fe2+_5_d_electrons" for the other Fe2+,
"Fe3+_0_d_electrons" for the Fe3+


- combine the orbitals using the small utility called combo, which you may obtain from Alex Granovsky's Firefly website.

- Manually paste the "alpha" and "beta" guesses  into a single $vec group, which would be the proper guess.

- cross all your fingers and toes, and expect it to converge into the proper state. If it does not converge, change convergers (SOSCF=.T. DIIS=.F.), onset of SOSCF (SOGTOL=1e-3) , etc.

- after SCF optimization using this guess, manually scramble the ordering of Fe atoms in your input, to ascertain whether a lower energy solution can be obtained with a different spin distribution.



Good Luck!

Thursday, January 16, 2014

Moving towards Open Access...

In physics and mathematics, publishing Preprints of papers in the arXiv is the most common form of distributing scientific papers. All the major journals in those areas have therefore been "forced" to accept papers previously available as preprints.
In Chemistry and Biology, however, most journals do not accept preprints and therefore authors are quite loath to make their work available as a preprint. The lack of this "free preprint" culture then enables journals to keep increasing their subscription prices way above inflation levels, which further gives publishers an extra incentive to keep rejecting sound work that might otherwise be available as costless preprints. This is a classic instance of Catch-22.
I believe that, as authors, we should do our utmost to fight this status quo. Our science should be evaluated on its merits, rather than on the accidental name of the journal where it has appeared. Therefore, I will henceforth submit all my Biochemistry work to PeerJ / PeerJPrePrints. PeerJ is an innovative and remarkably inexpensive Open Access Publisher with transparent peer-review and the option of publishing the paper's reviews alongside the manuscript.  The integrity of the reviewing process is therefore above reproach, ensuring that it will be both rigorous and fair.
PeerJ does not (yet?) accept submissions outside the field of Biology. My Chemistry work must continue to be submitted elsewhere. I am thinking of given the Beilstein Journal of Organic Chemistry a shot: completely free, open access, and rigorous. It does not have a stellar IF (around 2.8, I think), but who cares? Playing the IF game is ultimately detrimental to quick publication, as several journals insist on publishing only the "extra-sexy" work to prevent their IFs from falling, and often even refuse to send manuscripts for review simply because some editor feels they are not "hot" enough (ACS, I am talking to you....)

The power to change is, after all, in our hands. It may be a very small amount of power, and the odds of effecting any change may be vanishingly small, but if we do not use it, nothing will change for sure.

Wednesday, October 9, 2013

2013 Nobel Prize for Chemistry awarded to Warshel, Levitt and Karplus

This year, the Nobel Prize for Chemistry has a special flavor for computational biochemists, as the Swedish Academy has decided to recognize the creators of Quantum Mechanics/Molecular Mechanics hybrid methods. Levitt and Warshel developed the first computational simulation of a protein, back in 1975, whereas Karplus and his group developed the well-known CHARMm force-field and molecular dynamics code. I am very glad  to see Warshel recognized as the towering giant he really is (in spite of his short stature).  He is a very warm and likeable fellow, always eager for a good discussion on the merits (and demerits) of a scientific proposal. He does have, however, a singular lack of patience for bullshit, and a peculiar disregard for diplomatic niceties ....

Warshel's parents were Polish Jews who left Europe for Palestine before World War II to join a kibbutz. He attributes part of  his peculiar temper to the circumstances of growing up in such an utopian socialist community in the 1940's, before the Israeli War of Independence. Lying and "truth embellishment" were very strongly frowned upon, and one was expected to be able to withstand withering criticism whenever warranted. His BS-detector is therefore quite over-calibrated, and he takes no prisoners when arguing against a wrong-headed argument. Warshel's abrasive style is well-known in the computational chemistry, as are is frequent controversies with other workers.

He also told me one of the best jokes I know... He presented it as a real tale of his uncle's exploits as an officer in the Polish Army. here it goes:

During on of his official leaves, his uncle went to a brothel. After the "job" had been done, he got up to get dressed and leave. The prostitute the asked: "What about the money, sir?". And he replied: "An officer never accepts money, my lady"