Heating up a Protein, One residue at a time
Protein structures are fascinating things. Irregular in shape, but sturdy in design, proteins can undergo enormous changes in structure – they bend, spin, expand and pince. As such, proteins are sometimes called nano-machines. If we are lucky, we can catch the protein in flagranto, as certain small reactive molecules can induce a protein to switch between different motions. Some motions are very subtle.
Over the last year, I've been working on simulation methods to probe motions that involve only very slight changes in the structure of a protein. The work I've been doing is an extension of earlier work of a previous postdoc, Nobo Ota, in the Agard lab. Nobu had originally come up with the brilliant idea of freezing a protein, and then heating the protein at one single residue. By following where the energy would flow, he hoped to catch a glimpse of the subtle transfer of energy, and thereby understand something about subtle motions in the protein. He developed a method that he called Anisotropic Thermal Diffusion.
Nobu studied the PDZ domain from the 3rd domain of PSD-95 [1BE9], a very well studied protein. He first froze the PDZ protein to T=10K. Then, he pumped energy into a particular protein (green outline) at room temperature: