My work has used tools of physics to understand
how biological motor proteins convert biochemical fuel into mechanical
work. Using optical tweezers, we are able to manipulate single motor molecules
individually and to measure the nanometer scale motions these proteins
undergo. Using theoretical methods of statistical mechnanics, we can deduce
the molecular fuel economies and propose models for movement. In the funding
period starting 9/98, my work has yielded two major results. First, for
the molecular motor RNA polymerase, responsible for the transcription of
DNA into RNA, we have found that a simple tightly-coupled model for movement
quantitatively accounts for measured transcriptional velocities as a function
of applied load. The measurements were made with individual DNA templates
and single polymerases, and the model involves a series of biochemical
intermediates in the engine cycle followed by a thermally activated mechanical
transition. Second, we have made significant progress in understanding
the workings of the motor kinesin. Using a novel instrument, the optical
force clamp, and fluctuation analysis, which relies on the mathematical
theory of renewal processes, we have deduced the molecular fuel economy
of kinesin. Kinesin consumes only one ATP molecule for each 8 nm advance
it makes, even under loads up to 5 pN. Thus, the kinesin motor is tightly-coupled
(has no gears) and displays an energy efficiency up to 50%! |
