The conformational dynamics of the 10th type-III module of fibronectin (FN-III10) adsorbed on the perfect and three reduced rutile TiO2(110) surfaces with different types of defects was investigated by molecular dynamics (MD) simulations. Stable protein-surface complexes were presented in the four simulated models and were derived from the contributions of direct and indirect interactions of various functional groups in FN-III10 with the metal oxide layers. A detailed analysis to characterize the overall structural stability of the adsorbed FN-III10 molecule suggests that the bonding strength and the loss of protein secondary structure vary widely, depending on the topology of the substrate surface. The additional adsorption sites exhibiting higher activity, provided by the reduced surfaces, are responsible for the stronger FN-III10-TiO2 interactions, but too high an interaction energy will cause a severe conformational deformation and therefore a significant loss of bioactivity of the adsorbed protein.