First, I would like to thank Dr. Cannell for sharing his thoughts regarding our manuscript on the PLoS ONE web page. It is remarkable that work conducted in Maryland, and published on a web page administrated in California, can reach scientists in New Zealand. It seems that this is a clear indication that the PLoS model portends the future of scientific publishing!

I believe that Dr. Cannell’s hypothesis that our data might be explained if the interactions of the donor and multiple acceptor dipoles are not independent is quite plausible. We considered this possibility when we formulated our conclusion “that one of the theoretical assumptions on which the kinetic model prediction is based” might be incorrect, and we made a point of mentioning in the first paragraph of the introduction that FRET theory is based on the assumption “…that a donor interacts with each acceptor independently”. I must add, however, that I do not believe that our data proves this point, and I believe that several other explanations for our experimental results are also plausible. I eagerly await reading comments from others to hear alternative viewpoints, and hope that these comments can identify experiments that can be performed to test and differentiate between these possibilities.

I would also like to point out that currently in the biological FRET literature, the kinetic model remains the primary model used to interpret FRET measurements when multiple acceptors are present, and that this includes the assumption of dipole independence. Clearly, as Dr. Cannell pointed out, our study does call into question the generality of this approach.