I would start with apologizing for the delay in my previous post getting published. The session I wrote about was really on February 7th.
In that post I wrote about the size of this meeting taking me by surprise. The bad news is that this meant I missed a session today that I planned to attend for not getting my itinerary right. The good news is that I now have most of it figured.
I had a fantastic time listening to Dr. Marcos Sotomayor speaking about his research with cadherins. Cadherins are proteins necessary for hearing and balance. Cadherin-23 and Protocadherin-15 interacts to form what are known as tip links. Dr. Sotomayor has done extensive studies, both computational and experimental, studying the structural details of these cadherin complexes. The complexes form in a manner that is called an “extended handshake”. Imagine “shaking” hands with someone where you are holding the person’s arm right behind his/her palm (and vice versa). That is how these two proteins interact—one of them is slightly shifted with respect to the other.
One of his studies involved steered molecular dynamics (SMD) simulation to check the elasticity of these complexes. In SMD, an external force is applied to one or more atoms of the system of interest, and the response of the system under this force is studied. The objective of this study was to look at the ability of cadherin complexes to withstand the mechanical force generated by sound waves. These simulations have to be performed on the long, microsecond timescale. Remember that audible frequency is of the order of 20 kHz, and sub-microsecond timescale simulations would not be able to completely capture the influence of such frequencies. It was shown that Cadherin-23 and Protocadherin-15 forms a fairly stable complex (go loud music! We got robust stuff in our ears!)
It was also observed that the tip link becomes flexible in the absence of calcium. Atomic detail of the complex structure reveals a very strong glutamate-calcium interaction. Dr. Sotomayor has performed SMD simulations to measure the force necessary to break the complex apart. When the calcium is replaced with sodium, the complex can be broken much more easily (with lesser force). This hints at the importance of calcium in the mechanical strength of tip links.
That’s all from the morning session. Will be back with more shortly