Due to their role in chronic inflammation, allergies, autoimmune diseases and cancer, chemokines have become a target in drug discovery. Starting from existing structural data (PDB:
1ILP) of a chemokine interleukin-8
CXCL8 bound to a N-terminal peptide of its corresponding receptor CXCR1. We used the all-atom free-energy PFF02 on POEM@HOME to calculate the interaction energy differences between the wild-type complex and all alanine-exchanged peptides to determine the interaction hot spots. These changes are rationalized by decomposing the interaction energy differences into ther most impotant physical contributions.
The results of our analysis agree with available experimental functional assays, indicating that this approach is suitable for computational alanine screening and may help to identify competitive peptides as starting points for the development of inhibitors of protein-protein interactions for pharmaceutically relevant targets.
The following two graphs show the results for the docking simulations carried out on POEM@HOME.
These results were published in the Journal of Chemical Physics: Probing hot spots on protein-protein interfaces with all-atom free-energy simulation Irene Meliciani, Konstantin Klenin, Timo Strunk, Katja Schmitz, and Wolfgang Wenzel, J. Chem. Phys. 131, 034114 (2009), DOI:10.1063/1.3177008
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Anche se il progetto è in fase alpha è un risultato molto interessante.
P.S.: alleluiah, siamo di nuovo up.... per quanto? :no: