Date/Time
Date(s) - 01/05/2024
1:30 pm - 2:20 pm

Title: Integrated Modeling of Flexible Multi-Domain Protein Structures

Date: Wednesday May 1, 2024

Time: 1:30-2:20pm

Room: ABB 165

Host: Dr. Giuseppe Melacini

Abstract: Growth factor receptor-bound protein 2 (GRB2) is one of the critical proteins that recognize the tyrosine phosphorylation of the epidermal growth factor receptor (EGFR). Although the dimer conformation of GRB2 was determined using X-ray crystallography, the solution structure of GRB2 remains elusive due to its flexibility. Here, we have determined the structure ensemble of GRB2 in the monomeric form by integrating solution nuclear magnetic resonance (NMR) experiments, small-angle X-ray scattering (SAXS) measurements, and molecular dynamics (MD) simulations with Bayesian inferences. The two-step likelihood optimization is performed to integrate all the experimental and computational data of GRB2 conformation. Our methods demonstrate representative solution structures with high statistical weights, and we discuss the functional roles of the conformational dynamics of GRB2 in solution.