Thursday, September 29, 2011

Dividing research into very small chunks...

Research roductivity is most often measured by people who do not have the ability to distinguish good papers from bad papers. Such measurements therefore tend to devolve into mechanical algorithms that count the number of publications and the impact factor of the journal where the research was published, rather than sensible arguments about the merits (or demerits) of the researcher. Evaluating a researcher therefore becomes a "numbers games", where a researcher with a higher number of small papers easily outranks another who has a smaller number of longer, more complex, publications. The race to the "smallest publishable piece of research" increases the number of papers (arguably "good" to the researcher who needs a "good" evaluation) but makes accompanying the literature more difficult, as one has to keep track of ever increasing numbers of papers with dwindling individual importance. It also detracts from the value of research being reported: in my example today, two papers report computations of very similar compounds. The only difference is the interchange of a nitrogen with a phosphorus atom.
A single paper would have been much more useful and important, but research managers would count that as less productive :-(

PS: I happen to disagree strongly with the suggestion, in these papers, of the existence of intramolecular H-bonding, as the angles involved are too small for H-bonds.

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?

Coming soon to a worm near you....

Three possible stop codons are common in mRNA: UGA, UAA and UAG. These codons usually bind release factors, that prompt the release of of the nascent amino acid chain from the ribosome. Some organisms, however, contain tRNA complementary to one of these codons. In these organisms, that codon no longer triggers the ending of the translation process, but codes an amino acid instead. Several researchers have used this special tRNA to develop mutant cells with expanded genetic codes.Greiss and Chin have now taken this a step further: they have engineered a mutant strain of the worm C. elegans that translates every UAG codon as an artificial aminoacid. It was a complex endeavour (details are in their paper...) that surely would have deserved a well-publicized press conference :-)

Thursday, September 22, 2011

Puns and wordplay in Science

In 1975, E. M. Southern developed an elegant method to detect specific DNA after gel electrophoresis (J. Mol. Biol. 98, 503-517) . His technique soon became known as "the Southern blot", and the paper has so far gathered >35 thousand citations. This number is a dramatic under-estimate of the impact of Southern blot in the field of molecular biology, as the technique has became routine and "common knowledge", which means that most practitioners no longer cite the original paper. In 1977, a variation of the technique was developed by Alwine et al. to detect RNA. The name "Northern blotting" was soon proposed for their technique, as a wordplay on the original method. The application of a similar technique on proteins is called "Western blotting".

Naming methods (or variations) using wordplay is not limited to biochemical techniques. In computational chemistry, novel basis sets obtained from the well-known aug-cc-pVXZ basis set family by decreasing the number of polarization basis functions have recently been proposed by Don Truhlar. In a humorous touch, the aug- prefix (originally an abreviation of augmented) was considered an abbreviation of August. The new, smaller, basis sets aretherefore called apr-cc-pVXZ, may-cc-pVXZ, jun-cc-pVXZ and jul-cc-pVXZ. Not outright comedy material, but it does bring a quirky smile to your lips, right?

Tuesday, September 20, 2011

QM molecular dynamics

In classical molecular dynamics simulations, we follow the evolution of a system of particles that interact with each other according to newtonian mechanics. The correct description of chemical bonds, angles and torsions in classical mechanics can only be achieved by introducing carefully parameterized expressions that represent the change in electronic energy upon stretching/compressing a bond, or bending an angle. These parameterized force fields (AMBER, CHARMM, GROMOS, YASARA, OPLS) allow the simulation of very large systems (>10000 atoms) for long simulation times (>20 ns) with an obvious drawback: the quality of the simulations is only as good as the quality of the parameterized expressions, and therefore one is limited to the simulation of specific classes of previously characterized molecules/functional groups. Simulating chemical reactions is generally not possible without special protocols (like thermodynamic integration).

Ab initio molecular simulations (e.g. Car-Parrinello MD) are much more expensive, and are generally limited to (at most) a few dozen atoms and <100 ps. Two papers from Prof. Shogo Sakai's group show that QM molecular simulations can be performed with considerable time-savings if the system is partitioned into several smaller systems. They have not yet developed the theory to the point where one can attempt bond-breaking, but theirs seems a fruitful approach to the problem.