A Computational Analysis of the Sequence-Dependence of Protein-Peptide Binding Energies

Post date: Feb 15, 2023  by Katherine Menendez

Eukaryotic initiation factor 4E (eIF4E) is a protein that, concerted with other proteins such as eIF4G, binds to mRNA and initiates protein synthesis in eukaryotic cells. 4E-Binding Proteins (4E-BPs) are repressor proteins that compete with eIF4G and prevent translation. The main goal of this rotation project was to calculate and compare the binding energy of three peptide-protein complexes (two 4E-BPs and one 4Gs) using the MM-GBSA function in Maestro. Computational alanine scanning was used to find the "hot spots" residues in these peptides, amino acids with a high contribution to the binding energy.

Fig 2. Tridimensional structure of the complex: 4E-BP1- eIF4E (A), 4E-BP2- eIF4E (B) and eIF4GII- eIF4E (C) with each of the mutated variants. eIF4E is shown in green, and ligands in blue/brown.