Homology modelling: a review about the method on hand of the diabetic antigen GAD 65 structure prediction

This introductory paper describes the basic principles and clinical applications of the protein 3D structure prediction by homology modelling. The paper mainly addresses physicians and medical chemists. Because many proteins are of immediate clinical importance, the determination of their structures is crucial for molecular medicine. In homology modelling, a protein sequence with unknown structure is aligned with sequences of known protein structures. By exploiting structural information from the known configurations, the new structure can be predicted. The necessary condition for successful homology modelling is a sufficient similarity between the protein sequences. Because in the near future for every protein family at least one member with a known structure will be available, the importance and applicability of homology modelling is steadily increasing. We demonstrate the principles of homology modelling on hand of the Glutamic Acid Decarboxylase (GAD 65) structure prediction, which is a typical autoantigen involved in Diabetes Mellitus Type 1.