“A cord of three strands is not easily broken.” —Ecclesiastes 4:12Abu Simbel relief of Ramesses II shooting a composite bow at the Battle of Kadesh. Computational chemistry, like all attempts to simulate reality, is defined by tradeoffs. Reality is far too complex to simulate perfectly, and so scientists have developed a plethora of approximations, each of which reduces both the cost (i.e. time) and the accuracy of the simulation.

ICYMI: Ari and I announced our new company, Rowan! We wrote an article about what we're hoping to build, which you can read here. Also, this blog is now listed on The Rogue Scholar, meaning that posts have DOIs and can be easily cited. Conventional quantum chemical computations operate on a collection of atoms and create a single wavefunction for the entire system, with an associated energy and possibly other properties.

The Pauling model for enzymatic catalysis states that enzymes are “antibodies for the transition state”—in other words, they preferentially bind to the transition state of a given reaction, rather than the reactants or products. This binding interaction stabilizes the TS, thus lowering its energy and accelerating the reaction.

Since the ostensible purpose of organic methodology is to develop reactions that are useful in the real world, the utility of a method is in large part dictated by the accessibility of the starting materials.

TW: stereotypes about molecular dynamics. In his fantastic essay “The Two Cultures,” C. P. Snow observed that there was (in 1950s England) a growing divide between the academic cultures of science and the humanities: Literary intellectuals at one pole—at the other scientists, and as the most representative, the physical scientists.

An important problem with simulating chemical reactions is that reactions generally take place in solvent, but most simulations are run without solvent molecules. This is a big deal, since much of the inaccuracy associated with simulation actually stems from poor treatment of solvation: when gas phase experimental data is compared to computations, the results are often quite good.

TW: sarcasm. Today, most research is done by academic labs funded mainly by the government. Many articles have been written on the shortcomings with academic research: Sam Rodriques recently had a nice post about how academia is ultimately an educational institution, and how this limits the quality of academic research.

The concept of pK_a is introduced so early in the organic chemistry curriculum that it’s easy to overlook what a remarkable idea it is. Briefly, for the non-chemists reading this: pK_a is defined as the negative base-10 logarithm of the acidity constant of a given acid H–A: pK_a := -log₁₀([HA]/[A-][H+]) Unlike pH, which describes the acidity of a bulk solution, p

You are a scientist, not a lab monkey. You ought not to view your degree as “six years of hard labor in the chemistry mines.” Always make time to go to interesting seminars, talk with other people about their research, and read the literature. Otherwise, what’s the point of being a scientist? Only one person is really looking out for your best interests: you.

I’ve been pretty critical of peer review in the past, arguing that it doesn’t accomplish much, contributes to status quo bias, etc. But a few recent experiences remind me of the value that peer review provides: in today’s scientific culture, peer review is essentially the only time that scientists get honest and unbiased feedback on their work. How can this be true?