Zusammenfassung
Dieser Übersichtsartikel behandelt die Grundlagen und klinische Anwendungen der Protein-Strukturvorhersage mit der "Homology Modelling"-Methode. Der Artikel richtet sich vornehmlich an Mediziner und medizinische Chemiker. Da viele Proteine unmittelbar von klinischer Bedeutung sind, ist die Strukturbestimmung entscheidend für das Verständnis der molekularen Grundlage von Stoffwechsel, Signalübertragung, Immunreaktionen und damit assoziierten Krankheiten. "Homology Modelling" beruht auf dem Prinzip, dass Proteine mit ähnlichen Sequenzen hohe Strukturübereinstimmungen aufweisen. Dabei werden Informationen, wie Atomabstände, Bindungslängen, Bindungswinkel etc., über bereits bekannten Strukturen verwendet, um die unbekannte Proteinstruktur anhand ihrer Sequenz vorauszusagen. Da in Zukunft für jede Proteinfamilie mindestens ein Mitglied mit bekannter Struktur verfügbar sein wird, ist zu erwarten, dass Bedeutung und Anwendbarkeit der "Homology Modelling"-Methode weiter zunehmen werden. In dieser Arbeit werden die Grundlagen der Methode anhand der Strukturvorhersage des Enzyms Glutamate Decarboxylase (GAD 65) erläutert. GAD 65 spielt als Antigen bei Diabetes Mellitus Typ 1 eine entscheidende Rolle.
Summary
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.
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Wiltgen, M., Tilz, G. Homology modelling: a review about the method on hand of the diabetic antigen GAD 65 structure prediction. Wien Med Wochenschr 159, 112–125 (2009). https://doi.org/10.1007/s10354-009-0662-z
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DOI: https://doi.org/10.1007/s10354-009-0662-z