Surface layer protein, which is abundant in the gram-positive bacteria like Lactobacillus sp, for its adherence and symbiotic activity in the normal flora of gastrointestinal tracts. In this study, we showed the relative binding of the SlpAKB290, a homology-based model with a higher binding affinity to ErbB2 rather than the α, β-3integrin-binding domain through molecular docking. The critical binding affinity had been demonstrated with the protein-protein docked clusters’ flexibility and rigidity through the normal mode simulations and thermal unfolding to identify the constraint networks. The results showed a better performance SlpAKB290 with the ErbB2. The current study provided essential insight into the Lactobacilli sp.’s adherence to the host cells through protein-protein interactions.