A chemist and kinesiologist got on a bus, but this isn’t the set-up to a joke. Instead, kinesiologist and lead author Ned Debold and chemist Dhandapani Venkataraman, “DV,” began talking on their bus commute to the University of Massachusetts Amherst and discovered their mutual interest in how energy is converted from one form to another – for Debold, in muscle tissue and for DV, in solar cells.
An alternative energy source to replace the body’s usual one, a molecule called adenosine triphosphate (ATP, could control muscle activity, and might lead to new muscle spasm-calming treatments in cerebral palsy, for example, or activate or enhance skeletal muscle function in MS, ALS and chronic heart failure.
The usual approach to seeking a new compound is to systematically test each one among millions until one seems worth followup – the classic “needle in a haystack” says DV. “At one point I suggested to Ned, ‘Why don’t we build the needle ourselves instead?’ That started us on this interesting project that put together people who would otherwise never work together.” Computational chemist, Jianhan Chen, was invited to model interactions between the molecules DV was making and the myosin molecules Debold was using to test them.
Chen explains, “We did computer modeling because experimentally it is difficult to know how myosin might be using the molecules DV was synthesizing. We can use computer simulation to provide a detailed picture at the molecular level to understand why these compounds might have certain effects. This can provide insight into not only how myosin interacts with the current set of compounds, but also it can provide a roadmap for DV to use to design new compounds that are even more effective at altering myosin function.”
This month, the researchers report in the Biophysical Journal that they have made a series of synthetic compounds to serve as alternative energy sources for the muscle protein myosin, and that myosin can use this new energy source to generate force and velocity. Mike Woodward from the Debold lab is the first author of their paper and Xiaorong Liu from the Chen lab performed the computer simulation.
The next stage for the trio will be to map the process at various points in myosin’s biochemical cycle.