Rotation-induced Secondary Structure Losses and Bioactivity Changes of Bone Morphogenetic Protein-2 on Strontium-substituted Hydroxyapatite Surfaces

Abstract The manipulation of molecular structures and orientations of bone morphogenetic protein-2 (BMP-2) upon biomaterials is of great significance in bone tissue engineering. In this study, the adsorption dynamics and molecular structures of BMP-2 upon a series of strontium-substituted hydroxyapatite surfaces (Sr-HAPs) were systemically investigated by molecular dynamics (MD) simulations. Intriguingly, BMP-2 was rotated by 45 degrees to further explore the influence of protein orientations on the adsorption behaviors and biological activity of BMP-2. The results revealed that the interaction energy, number of contacts, and contact area between BMP-2 and Sr-HAPs were significantly bigger than the pristine HAP, which suggests that Sr-HAPs owned higher binding affinity of BMP-2 molecules. Moreover, the molecular conformation, stability of cysteine-knots, and secondary structures of BMP-2 were notably influenced by the Sr content. Interestingly, rotating BMP-2 by 45 degrees (especially BMP-ya45) obviously weakened the adsorption capacity and secondary structures, which probably leads to inactivation of the adsorbed BMP-2 proteins. This work deeply clarified that the rotation of proteins could induce serious changes of secondary structures and biological function during the adsorption process of BMP-2 upon Sr-HAPs, which can provide theoretical guidelines for a high-efficiency and high-bioactivity immobilization of BMP-2 upon biomaterial surfaces for bone regeneration.