In a recent work to appear in Protein Science (see this post) we have worked with Dr. Daniele di Marino and collaborators in Italy and Belgium to predict the elusive structure of the complex between the Cytoplasmic Fmrp Interacting Protein 1 (CYFIP1) and the eukaryotic translation initiation factor 4E (eIF4E). This interaction is known to be disrupted in people affected by Fragile X syndrome, one of the major causes of autism in children. Researchers have not been able to solve the structure of this complex by experimental means. In this work, illustrated below by means of movies of molecular dynamics trajectories, we have obtained what we believe is a very good guess of how these two proteins might be interacting.
This work has been made possible by the WEB Computing Grid at Brooklyn College. Thanks!
The structure of the CYFIP1p-eIF4E complex is predicted by parallel BEDAM conformational search. CYFIP1p is found to bind in the same region as other known peptide inhibitors, but in a unique orientation.
The predicted structure showed remarkable stability during 50 ns of explicit solvent molecular dynamics with the Desmond program (DE Shaw Research, New York, NY). In contrast, the CYFIP1 peptide unfolded when prepared in other poses.