Mimicking trimeric interactions in the aromatic side chains of the proteins: A gas phase study of indole…(pyrrole)2 heterotrimer JCP: BioChem. Phys. 6, 05B601 (2012) Mimicking trimeric interactions in the aromatic side chains of the proteins: A gas phase study of indole…(pyrrole)2 heterotrimer J. Chem. Phys. 136, 174302 (2012) Ligand migration in myoglobin: A combined study of computer simulation and x-ray crystallography JCP: BioChem. Phys. 6, 04B620 (2012) Ligand migration in myoglobin: A combined study of computer simulation and x-ray crystallography J. Chem. Phys. 136, 165101 (2012) Deoxycholate induced tetramer of αA-crystallin and sites of phosphorylation: Fluorescence correlation spectroscopy and femtosecond solvation dynamics JCP: BioChem. Phys. 6, 04B614 (2012) Additional information on J. Appl. Phys. Whispering gallery mode (WGM) optical biosensors are capable of extraordinarily sensitive specific and nonspecific detection of species suspended in a gas or fluid. Recent experimental results suggest that these devices may attain single-molecule sensitivity to protein solutions in the form of stepwise shifts in their resonance wavelength, k R , but present sensor models predict much smaller steps than were reported. This study examines the physical interaction between a WGM sensor and a molecule adsorbed to its surface, exploring assumptions made in previous efforts to model WGM sensor behavior, and describing computational schemes that model the experiments for which single protein sensitivity was reported. The resulting model is used to simulate sensor performance, within constraints imposed by the limited material property data. On this basis, we conclude that nonlinear optical effects would be needed to attain the reported sensitivity, and that, in the experiments for which extreme sensitivity was reported, a bound protein experiences optical energy fluxes too high for such effects to be ignored. V C 2012 American Institute of Physics.