Showing posts with label ambiguity. Show all posts
Showing posts with label ambiguity. Show all posts

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.

Tuesday, November 29, 2011

The limits of homology modeling

The computational prediction of three-dimensional structures of protein sequences may be performed using a wide variety of techniques, such as homology modeling or threading. In threading, the correct fold is searched for by evaluating the energy of the intended sequence when it is "forced" to adopt each of the known folding patterns. In homology modeling, one looks for a high-similarity protein sequence with experimentally-determined 3D structure, and mutates it in silico until the desired sequence is obtained. Many different programs and web-servers are now available for these tasks, differing among themselves in the forcefields used, alignment algorithms, etc. Performance is usually quite good when templates with similarity >40% are used.

Recently, two small proteins with very high homology (>95%) but widely differing structure have been designed and studied. Starting from a pair of proteins with < 20 % identity and different 3D structures, the authors gradually mutated one sequence into the other, and ended up generating two sequences differing only in one amino acid, but with different folds. Attempts to unravel the precise mechanisms governing the selection of one fold over the other have however been inconclusive, because current molecular dynamics protocols and force fields are not accurate enough to measure the small energy differences involved.

Tuesday, September 27, 2011

What's in a name?

The IUPAC distinguishes "Lewis acidity" from "electrophilicity": the first concept relates to the equilibrium constant of the reaction of an electrophile (i.e. the termodynamics), whereas electrophilicity is related to the rate constant (i.e. the kinetics) of the reaction. However, the actual usage of the words in ordinary chemical parlance is somewhat more ambiguous, as the concepts are often used interchangeably.
A recent paper on this topic "Separating Electrophilicity and Lewis Acidity: The Synthesis, Characterization, and Electrochemistry of the Electron Deficient Tris(aryl)boranes B(C6F5)3–n(C6Cl5)n (n = 1–3)" caught my attention. However, this paper does not compare the changes in thermodynamics vs. kinetics ofthe title compounds upon increasing n. It rather compares their Lewis acidity with their ability to capture an electron (which the authors call electrophilicity). Quite a difference, don't you think?