4. The physiological concentration is a bit misleading. First, its clear now that cells have microenvironments, and 'physiological' concentrations are hard to define. Also, in a cell, I think (and I think others tend to agree) that kD plays little role at the end. kD is a combination of k(on) - which is concentration dependent but in a cell very likely diffusion limited - and of k(off) which I think is what matters most in the cell.
Can you provide some references about kD not mattering in cells? I had thought it a basic tenet that kD was a major indication of physiological relevence. After all, one could presumably determine a kD for any two proteins, so the order of magnitude of the kD would seem to matter. I hear that your argument is more subtle in considering the elements of kD, but isn't kD usually a rough indicator of k(off), and of course more readily-accessible experimentally? I am intrigued by the idea...
Jacob Keller
