by Angela Herring

We all know—generally speaking—how a car works: The gas pedal makes it go, the break pedal makes it stop, and the steering wheel deter­mines its course. But pop open the hood and you’ll find there’s a lot more nuance to those maneuvers.

With macro­scopic machines, get­ting under the hood is a straight­for­ward process, but when it comes to the mol­e­c­ular machines dri­ving bio­log­ical func­tions inside our cells, things get a lot more com­pli­cated, according to Paul Whit­ford, an assis­tant pro­fessor of physics.

That’s because the envi­ron­ment in which they operate has a much greater impact on the machines them­selves. For example, water mol­e­cules are con­stantly bom­barding them, and since the energy of a water mol­e­cule is very close to that of the mol­e­c­ular bonds in these micro­scopic machines, the impact is significant.

Whit­ford equates it to a car that moves from the force of wind alone. “Imagine you have to wait for random gusts of wind to push you over a moun­tain. That would be a very inef­fi­cient way of dri­ving, but that’s how micro­scopic machines work,” he said. “The ques­tion we are asking is: What are the prop­er­ties of those random kicks that guide the machine’s movement?”

A com­put­er­ized depic­tion of the e. coli ribo­some. The small spheres rep­re­sent charged par­ti­cles in the sur­rounding envi­ron­ment. Image by Paul Whitford.

In a paper recently pub­lished in the journal PLoS Com­pu­ta­tional Biology, Whit­ford and col­lab­o­ra­tors from Cor­nell Med­ical School, Uni­ver­sity of Cal­i­fornia, Berkeley, and Los Alamos National Lab­o­ra­tory present a com­pu­ta­tional frame­work that esti­mates those random kicks for the mol­e­c­ular machine known as the ribo­some. Via a process called translo­ca­tion, ribo­somes make pro­teins from the instruc­tions given inRNA. Without them, life would not be pos­sible, Whit­ford said. But we have very little idea of the phys­ical prin­ci­ples that guide their func­tion, that is, we don’t know what’s going on under the hood.

Ribo­somes con­sist of hun­dreds of thou­sands of atoms arranged in a very com­plex struc­ture, which was only deter­mined in the early 2000s after sev­eral decades of study. With that struc­ture in hand, along with advanced com­pu­ta­tional tech­niques, and an under­standing of the processes that occur around the ribo­some, researchers are now able to study the spe­cific atomic inter­ac­tions within the enor­mous struc­ture. According to Whit­ford, they can use this infor­ma­tion to esti­mate how the ribo­some will change its con­for­ma­tion over time.

Whitford’s team obtained a sim­u­la­tion of the ribo­some in action for more than 1.3 microseconds—roughly five times longer than the lab’s pre­vious record-​​breaking sim­u­la­tion. The cal­cu­la­tion took sev­eral months and required the use of two supercomputers—the NMCACEncanto Super­com­puter in New Mexico and the TACC Lon­estar Super­com­puter in Texas.

The com­pu­ta­tional frame­work pre­sented in this research will be a useful tool for exper­i­mental biol­o­gists studying the ribo­some, Whit­ford said. Having this ground-​​level under­standing of the machine, exper­i­mental data about the kinetics and ener­getics of ribo­somal processes can now be com­pared in a mean­ingful way, essen­tially allowing exper­i­men­tal­ists to con­nect the gas pedal’s func­tion to the engine. Assis­tant pro­fessor Paul Whit­ford uses com­pu­ta­tional tech­niques to study the nuances of micro­scopic machines like the ribo­some, which is respon­sible for pro­tein syn­thesis.

Originally published in news@Northeastern on March 22, 2013