This article is part of the supplement: Italian Society of Bioinformatics (BITS): Annual Meeting 2007

Open Access Open Badges Research

In silico docking of urokinase plasminogen activator and integrins

Bernard Degryse1, Juan Fernandez-Recio2, Valentina Citro3, Francescol Blasi1 and Maria Vittoria Cubellis3*

Author Affiliations

1 San Raffaele Scientific Institute, Milan, Italy

2 Life Sciences Department, Barcelona Supercomputing Center, Spain

3 Dipartimento di Biologia strutturale e funzionale, Universita' di Napoli“Federico II”, Italy

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BMC Bioinformatics 2008, 9(Suppl 2):S8  doi:10.1186/1471-2105-9-S2-S8

Published: 26 March 2008



Urokinase, its receptor and the integrins are functionally associated and involved in regulation of cell signaling, migration, adhesion and proliferation. No structural information is available on this potential multimolecular complex. However, the tri-dimensional structure of urokinase, urokinase receptor and integrins is known.


We have modeled the interaction of urokinase on two integrins, αIIbβ3 in the open configuration and αvβ3 in the closed configuration. We have found that multiple lowest energy solutions point to an interaction of the kringle domain of uPA at the boundary between α and β chains on the surface of the integrins. This region is not far away from peptides that have been previously shown to have a biological role in urokinase receptor/integrins dependent signaling.


We demonstrated that in silico docking experiments can be successfully carried out to identify the binding mode of the kringle domain of urokinase on the scaffold of integrins in the open and closed conformation. Importantly we found that the binding mode was the same on different integrins and in both configurations. To get a molecular view of the system is a prerequisite to unravel the complex protein-protein interactions underlying urokinase/urokinase receptor/integrin mediated cell motility, adhesion and proliferation and to design rational in vitro experiments.