Submitted to the faculty of the Bioinformatics Graduate Program in partial fulfillment of the requirements for the degree Master of Science in the School of Informatics, Indiana University December 2005 / The last decade has witnessed numerous proteomic studies which have predicted and successfully confirmed the existence of extended structurally flexible regions in protein molecules. Parallel to these advancements, the last five years of structural bioinformatics has also experienced an explosion of results on molecular recognition and its importance in protein-protein interactions. This work provides an extension to past and ongoing research efforts by looking specifically at the “flexibility and disorder†found in protein sequences involved in molecular recognition processes and known as, Molecular Recognition Elements or Molecular Recognition Features (MoREs or MoRFs, as we call them). MoRFs are relatively short in length (10 – 70 residues length); loosely structured protein regions within longer sequences that are largely disordered in nature. Interestingly, upon binding to other proteins, these MoRFs are able to undergo disorder-to-order transition. Thus, in our interpretation, MoRFs could serve as potential binding sites, and that this binding to another protein lends a functional advantage to the whole protein complex by enabling interaction with their physiological partner. There are at least three basic types of MoRFs: those that form α-helical structures upon binding, those that form β-strands (in which the peptide forms a β-sheet with additional β-strands provided by the protein partner), and those that form irregular structures when bound. Our proposed names for these structures are α-MoRF (also known as α-MoRE, alpha helical molecular recognition feature/element), β-MoRF (beta sheet molecular recognition feature/element), and I-MoRF (Irregular molecular recognition feature/element), respectively. The results presented in this work suggest that functionally significant residual structure can exist in MoRF regions prior to the actual binding event. We also demonstrate profound conformational preferences within MoRF regions for α-helices. We believe that the results from this study would subsequently improve our understanding of protein-protein interactions especially those related to the molecular recognition, and may pave way for future work on the development of protein binding site predictions. We hope that via the conclusions of this work, we would have demonstrated that within only a few of years of its conception, intrinsic protein disorder has gained wide-scale importance in the field of protein-protein interactions and can be strongly associated with molecular recognition.