Computer aided design and NMR characterization of an oligopeptide targeting the Ebola virus VP24 protein

The Ebola viral Protein 24 (VP24) inhibits interferon signaling through its interaction with the human protein Karyopherin, thus impairing the immune response of the host against the infection and increasing its rate of diffusion into the organism and its lethality. This makes VP24 a potential pharmacological target, as the inhibition of its interaction with Karyopherin could reduce Ebola virulence. In this work, we carried out an atomic level study of the network of interactions between VP24 and Karyopherin using molecular dynamics and computational alanine scanning. Modeling the VP24-Karyopherin complex allowed us to identify the amino acid residues responsible for protein-protein binding and led to the identification of a nonapeptide with VP24 binding potential. Subsequently, the ability of this peptide to actually bind VP24 in solution has been assayed using Saturation Transfer Difference NMR and Circular Dichroism. Experimental and molecular modeling data concerning the VP24-peptide complex have been compared and putative peptide binding sites and modes are discussed.