Escherichia coli (E. coli) K1 is the most common Gram-negative bacteria causing neonatal meningitis, but how E. coli penetrate the blood-brain barrier remains elusive. Discovering the binding pattern of IbeA and its host receptors on Human Brain Microvascular Endothelial Cell (HBMEC) is a critical thing for development of meningitis pathogenesis. Recently, our lab has just reported a key host receptor, Caspr1, could directly interact with IbeA through the extracellular domain, and this interaction activated host focal adhesion kinase signaling causing E. coli internalization into the HBMEC. In the present study, the interaction between Caspr1 and IbeA was predicted by an integrated protocol, which combines molecular homology modeling, protein–protein docking, molecular dynamics (MD) simulations, InterProSurf method, alanine scaning and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) binding free energy calculations. All the Trajectory file of simulations for this project were listed and shared here.