Life is like chem, ’cause the goal’s to be able
To bond well with others so we can be stable
Poetry has always had a lot to say about romance, describing how two people meet and feel a spark of connection, and everything that follows. Computational Biophysical Chemist Mala L. Radhakrishnan found that she could use poetry to express a different (but also surprisingly similar) connection. She writes poems which describe connections found in chemistry, including the bonds between atoms and the binding between a drug and its receptor.
How did a chemist become a poet? It all started when Radhakrishnan was working with Teach for America, soon after graduating from Harvard College, where she majored in chemistry and physics. She got permission for her students to paint chemistry murals on the walls of the school building, which would soon be gutted. A group of them created a soap opera-like painting about a sodium ion and a chloride ion who wanted to get together. Their break-up also involved some magnesium and “showed an understanding of the basic ideas of ionic bonding” while also proving to be “creative and humorous.”
Around the same time, Radhakrishnan’s friend brought her to the Boston Poetry Slam at the Cantab Lounge, where they dared each other to participate in an open mic. After trying a few more typical poems, the science teacher decided to try one about chemistry. Soon, she found herself using poetry all the time to help her students and other readers of her poems understand concepts like the law of thermodynamics.
Radhakrishnan has found that personifying atoms and molecules in her poems helps people learn and shows just how romantic, dramatic, and sometimes comedic chemistry can be. “At the molecular level,” she says, “chemistry is just a soap opera.”
As a computational biophysical chemist, Radhakrishnan investigates the interactions between large biological molecules in the human body and other molecules that are designed to bind with them to treat diseases. She has worked on HIV drugs and helped analyze potential molecular treatments for Alzheimer’s disease that inhibit a kinase (a protein involved in cellular growth) that might be connected to the syndrome. She also studies drugs which treat chronic myeloid leukemia by inhibiting another kinase that causes the cancer’s uncontrolled cell growth when left unrestrained.
When she is working on one of these projects, Radhakrishnan’s creativity expresses itself in both chemical processes and the ways she describes them. She sees herself as a “matchmaker” or a “marriage counselor” for the molecules she studies. What qualities would a drug need to make it bind more easily to the molecule it is targeting? She needs to know which aspects of the drug are relevant and which aren’t, just like if you were trying to predict whether two people are compatible. Some information would be very relevant to answer this question, like where the people want to live. But the question “Is your second toe longer than your first toe?” isn’t as helpful.
A lesson from chemistry we should all take:
Let us be judged by the bonds that we make
The qualities that enable a drug molecule to bind to its target in the human body might not be obvious. For example, since positive charges attract negative charges, one would think that for a negatively-charged target, it’s best to make your drug as positively-charged as possible to make it bind better. But in the human body, molecules are surrounded by water. Water (H2O) is a polar molecule, meaning that it has a partially positive end (its hydrogen atoms) and a partially negative end (its oxygen atom). The more charged your drug is, the more the water surrounding it will be attracted to it, “sticking” to it like glue and getting in the way of the molecule it was meant to bind to.
To get the charge just right and attract the intended molecule without attracting too much water, Radhakrishnan uses lots of calculus. Picture a curve that slopes down, reaches as low as it can go, and then goes back up again. Calculus allows you to find the slope of that curve, including the point where the slope of the curve is zero – the minimum, where you’ve gone as low as you can. Radhakrishnan uses calculus to find the minimum amount of energy required (or the maximum amount of energy released) when two molecules come together to bind. Generally, her work requires an “engineering mindset: optimization helps us improve on drugs.”
Making molecules compatible isn’t the only thing Radhakrishnan has to think about. She also has to make sure that the drugs she studies aren’t so good at their jobs that they end up binding to and inhibiting other molecules besides the ones she is targeting. In other words, they need to be “specific” (choosy). Drugs that are too “promiscuous” (binding with many molecules because they are not choosy enough) might end up targeting healthy molecules that the body needs to function, causing unpleasant side effects.
Chemistry: it’s ok to find it confusing
Yet also beautiful, useful, amusing!
On the other hand, drugs that are too specific might become ineffective if their targets mutate, changing their shape or charge distribution enough that drugs can no longer bind to them. That’s how bacteria become resistant to antibiotics (some antibiotics are too specific, targeting older variants of the bacteria but not newer mutations). Drugs work best when they are both specific and promiscuous.
Her interest in combating drug resistance is part of what led Radhakrishan to research peptides, which “bind to more generic places on bacteria” and “could become an alternative to traditional antibiotics.”
Radhakrishnan and her students analyze potential medicines with a modeling technique called molecular dynamics simulation. They use the model to create realistic “movies” that show the interactions between drugs and their targets.
Molecular dynamics simulations use lots of math, calculating quantities like the velocities of each atom in the molecules and the forces acting on each one. Chemists plug those velocities and forces into the equations of physics to determine where each atom will end up a very short time (perhaps measured in femtoseconds1) later. These calculations are repeated many times over to create each frame of the movie. The movie itself shows events lasting between only nanoseconds (billionths of a second!) to a microsecond (a millionth of a second), along distances of only angstroms (10-10 meters) to nanometers (10-9 meters).
Radhakrishnan is fascinated by how the models she and her colleagues create can be useful despite their limitations. “I love the fact that models are human-made, totally fictional, and yet we use them to learn true things about the world.” They are capable of predicting real things and helping real people.
As a child, Mala was excited by science, loving to go to science exhibits with her father, who was trained as a mechanical engineer. She never thought of science as merely memorizing facts, but recognized how it is all about creativity. She liked math as well, especially calculus, though algebra felt frustratingly boring … until she realized it could be used as a means to an end to investigate other, fascinating subjects.
Just as the molecules she studies often behave differently in environments crowded with water and other molecules than they do on their own, Mala found herself adapting to the crowd, loving to participate in her school’s math team but hiding in the corner there and eventually abandoning it in high school because it didn’t seem “cool.” But she’s come a long way from there, now enthusiastically teaching math and science to her students and learning new things herself along the way. She couldn’t be happier to share and teach about the poetic, romantic and fun world of chemistry!
What I’d give to be whole like that.
Everyone counts on the number 10:
Little Billy’s counting his fingers.
A diver receives a perfect score.
Little Jane does 5*3,
(even if incorrectly.)
But nobody ever needs me,
Or can even write me down.
Infinitesimally higher than 10,
Infinitely lower in value.
I’m simply inconceivable.
And since they cannot understand me,
They cast me away as “irrational.”
Thoughts of 10.00203748391650982736928374637…
Mala L. Radhakrishnan
1 A femtosecond is a quadrillionth of a second. Having trouble imagining how fast that is? We are, too! Think of how fast a millionth of a second might be. Then split the millionth of a second (called a microsecond) into a billion pieces: one of those tiny pieces of a second is a femtosecond. A femtosecond is a billion times faster than a microsecond. It’s also a million times faster than a nanosecond (there are a billion nanoseconds in one second). Femtosecond measure the speeds of movements within molecules. Lasers helped scientists begin to experimentally measure processes on the femtosecond time scale.