One key feature of living systems is that biochemical processes are strictly regulated. Disruption of such regulation often leads to serious diseases. Therefore, understanding the regulation mechanism is of great importance. In most cases, regulation is introduced through a conformational change induced by ligand binding (e.g. metal ion) or chemical modification (e.g. phosphorylation). It should be noted that the induced conformational change is not necessarily large in scale, and therefore the coupling between such a conformational change and subsequent chemical steps must be tight for the signaling cascade to occur. How such "signal amplification" occurs at an atomic level is not always clear from experimental data alone. Computational work, once again, can provide valuable insights into such issues.

One interesting system that we propose to study is aequorin, a bioluminescent protein found in jellyfish. It is activated by calcium ions, and emits a blue light of 470nm. Due to its high sensitivity to Ca2+, aequorin has been widely used an indicator of intercellular calcium concentrations. Although speculations have been made on the mechanism of the luminescent process long ago, detailed understanding of aequorin was made possible only recently due to the available high-resolution x-ray structure. Based on the structure, it was proposed that the luminescent reaction is initiated by a conformational change around the C terminus, which is caused by the binding of calcium ions. However, a detailed knowledge about the activation process is still lacking, and theoretical analysis can be very useful in providing the missing link. The effect of active site residues, mainly histidine and tryptophan, have been investigated with mutation studies. The most interesting result is related to the W86Y mutant, which gave a bimodal emission spectrum. It was speculated that different protonation states of the excited chromophore are involved, although no detailed scenario was given. Finally, one interesting question is the role of protein dynamics on the emission spectrum, i.e. the mechanism of energy partitioning during the generation of chromophore. Related issues have been studied in detail for chemiluminescent processes both experimentally and theoretically in small gas phase systems. Understanding these detailed mechanisms of bioluminescence is not only of fundamental value, but also can be useful in engineering novel bio-indicators for species other than calcium in cell.