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?

Friday, July 18, 2014

How biased are you, when you check the literature?

As scientists, we tend to think of ourselves as (at least) a little less biased than the average person. However, we still have to rely on mental shortcuts to classify information regarding its importance, relevance and trustworthiness. These shortcuts allow us to survive among the wealth of information we take from our environment, but are also prone to over-simplification and inevitably lead to bias. When I browse my RSS feeds, or the lists of hits in a PubMed or Web of Science query, I have found myself to be unexplainably biased against papers with only Indian, Persian or Chinese author names, but not against papers which only have Thai, Serbian, or Russian names. It is a "gut" reaction, with no input from the "reflective" portion of my brain. All I can do is be aware of it, and make an extra effort  to engage my thinking brain when this happens. This is the reason I have lately become convinced of the importance of enabling double-blind peer review: of course any author would be able to drop enough hints in the text to make their identity obvious, but forcing the referee to start reading the manuscript without any "mental baggage" (either for or against it)  might help researchers from disadvantaged institutions/countries overcome the biases that now play strongly against them

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.