Energy migration in self-assembled, water soluble, quantum dot (QD) nanoclusters is reported. These spherical nanoclusters are composed of CdSe QDs bound together by pepsin, a digestive enzyme found in mammals. A structural model for the clusters is suggested, based on scanning transmission electron microscopy, as well as dynamic light scattering and small angle X-ray scattering. Cluster sizes range from 100 to 400 nm in diameter and show a close-packed interior structure. Optical characterization of the absorption and emission spectra of the clusters is reported, finding photoluminescence quantum yields of up to approximately 60% in water for clusters made from core-shell CdSe-ZnS QDs. Clusters prepared from two different size populations of CdSe QD samples (3 and 4 nm in diameter) demonstrate energy migration and trapping. Resonance energy transfer (RET), from small to large dots within the QD-pepsin cluster, is observed by monitoring the quenching of the small donor dot fluorescence along with enhancement of the large acceptor dot fluorescence.