Thursday, June 16, 2016

Planned papers (update 2)

Overall progress on my planned manuscripts:
  • the reactivity of P450 compound I towards 1,2-dihydroazaborines: in review
  • electron-transfer to oxygen vs. singlet-triplet crossings in a cofactor-free dioxygenase  submitted to PeerJ on June 16th
  • the influence of solute-solvent dispersion/repulsion interactions on the behavior of molecular torsion balances.  No progress since last update. I doubt this could ever become publishable :-(
  • the binding of rubromycin derivatives to telomerase and DNA polymerase. Analysis of the last 100 ns MD mostly complete
  • analysis of molecular determinants of inhibitor binding to monoamine oxidases A and B Analysis of the MD simulations almost complete
  • the reaction mechanism of copper-catalyzed addition of azides to iodoalkynes. No progress since last update
  • the reaction mechanism of copper-catalyzed aldol synthesis described by Marek No progress since last update
  • reactivity of MerB towards p-block organometallic compounds No progress since last update
  • computational develoment of lead compunds for inhibition of plasmid-borne DHFR No progress since last update 
  • computational development of inhibitors of anthrax protective antigen cleavage by furin.  No progress since last update
     
     

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, April 22, 2016

Planned papers (update 1)


It is said that "No battle plan ever survives contact with the enemy". In my case, the enemy is myself: a permanent inclination towards procrastination, often disguised as an urge to delve deeper into tangentially relevant (or even irrelevant) literature, or to run a new series of computations in yet another interesting system.

And so it came to pass that my plans to increase my manuscript production predictably advanced much more slowly than I had envisioned. In my defence, I can only say that the writing process showed that a few of my computations were not as complete as I expected: a few single-points had converged into an excited state, a couple of transition states had to be newly optimized, etc. But I finally managed to get one manuscript almost ready.

Overall progress on my planned manuscripts:
  • the reactivity of P450 compound I towards 1,2-dihydroazaborines: Available as a preprint here
  • computational develoment of lead compunds for inhibition of plasmid-borne DHFR Introduction/Methods section complete. Results tables and graphs ready
  • computational development of inhibitors of anthrax protective antigen cleavage by furin. No progress
  • the influence of solute-solvent dispersion/repulsion interactions on the behavior of molecular torsion balances.  Analysis of the results does not show any consistent improvement of the fit of computation with experiment upon inclusion of dispersion/repulsion interactions between implicit solvent and solutes
  • the binding of rubromycin derivatives to telomerase and DNA polymerase. Found serious shortcomings in my AutoDock computations. I have now repeated everything with AutoDock Vina, including flexibility of aminoacid sidechains. 100 ns MD now finishing for three ligands in three candidate binding poses.
  • the reaction mechanism of copper-catalyzed addition of azides to iodoalkynes. No progress
  • the reaction mechanism of copper-catalyzed aldol synthesis described by Marek No progress
  • analysis of molecular determinants of inhibitor binding to monoamine oxidases A and B No progress
  • reactivity of MerB towards p-block organometallic compounds No progress
  • electron-transfer to oxygen vs. singlet-triplet crossings in a cofactor-free dioxygenase  Introduction/Methods section complete. Results tables and graphs ready




Friday, January 1, 2016

Planned papers for 2016

Last year, Jan Jensen published his publication plans for 2015. I will do the same this year, mostly as a way to force myself to stop procrastinating, as I have a large backlog of research which is ready for publication  (except fo the pesky little detail that I have not started to write the papers).
So here it goes.... This year, I plan to submit my research on :
  • the reactivity of P450 compound I towards 1,2-dihydroazaborines
  • computational develoment of lead compunds for inhibition of plasmid-borne DHFR
  • computational development of inhibitors of anthrax protective antigen cleavage by furin
  • the influence of solute-solvent dispersion/repulsion interactions on the behavior of molecular torsion balances
  • the binding of rubromycin derivatives to telomerase and DNA polymerase
  • the reaction mechanism of copper-catalyzed addition of azides to iodoalkynes
  • the reaction mechanism of copper-catalyzed aldol synthesis described by Marek
  • analysis of molecular determinants of inhibitor binding to monoamine oxidases A and B
  • reactivity of MerB towards p-block organometallic compounds 
  • electron-transfer to oxygen vs. singlet-triplet crossings in a cofactor-free dioxygenase 

I will force myself to update this list with a progress report every month. Let's see if I can "shame myself" into getting  my thoughts in paper :-)

 

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.