Like a car engine from space

Image via Paul Whitford.

So let’s pre­tend that your car wasn’t built by human hands, but just kind of landed in your dri­veway one day, after a morning drive through outer space. You, and auto-​​mechanics every­where, have no idea how it works and get­ting around that is made par­tic­u­larly dif­fi­cult because you can only get under the hood when it’s not running.

These are the gen­eral cir­cum­stances that assis­tant pro­fessor Paul Whit­ford faces when trying to model the behavior of mol­e­c­ular machines like the ribo­some, a cel­lular com­plex made out of RNA and pro­teins that is respon­sible for pro­tein pro­duc­tion. Using tech­niques like x-​​ray crys­tal­log­raphy and cryo-​​electron microscopy, sci­en­tists have static pic­tures of what the ribo­some looks like at par­tic­ular points during its activity, but they can never look directly under the hood, so to speak.

To get around that fact, Whit­ford uses a few stan­dard bio­phys­ical prin­ci­ples — like the fact that atoms can’t pass through one another and the fact that water mol­e­cules are con­stantly bom­barding every­thing inside the cell — to gen­erate com­puter models that can elu­ci­date what’s going on in between the snapshots.

Below is a video he made a couple years ago from a study that appeared in the journal RNA, which served as the foun­da­tion for their sub­se­quent studies appearing in Nature and Pro­ceed­ings of the National Academy of Sci­ences. It shows exactly how one piece of the ribo­some (tRNA) moves from one side of the com­plex to the other. The infor­ma­tion can help drug devel­opers make mol­e­cules that are more likely to interact and have the impact they’re going for.

It also shows just how dif­fi­cult life is at that small scale. Your car engine doesn’t have to worry about things like wind dis­rupting its func­tioning, but ribo­somes are always at the mercy of the sur­rounding envi­ron­ment, which is con­stantly in flux. The ner­vous tremors you’ll see are a result of those bom­barding water mol­e­cules.