| The adsorptions of protein on different substrate are widely applied in various fields, such as biomaterials, biomedical devices, biosensors, biomimetic materials and so on. Polylactic acid (PLA) is widely used as biomedical material due to its biocompatibility, it can be made as scaffolds to treat bone injury. The bone morphogenetic proteins (BMPs) adsorption on these implant surfaces induces bone and cartilage formation at implant site. The knowledge on the protein/surface interaction is crucial to designing well biomaterials and biosensors. In recent decades, many experimental methods have been employed to discuss the adsorbed amounts of proteins on solid surfaces and protein structural reorganization etc. However, it is still very difficult to understand the interaction mechanism between protein and substrate from molecular level through experimental methods. As a bridge between theoretical and experimental, molecular simulation can provide an effective way to explore protein adsorption phenomenon and interaction from molecular view.In this thesis, Classical molecular dynamics (MD) simulations and steered molecular dynamics (SMD) were employed to investigate the adsorption/desorption behavior of BMP-2/BMP-7on PLA and its copolymers. The influence of hydrophilic/hydrophobic on their adsorption/desorption and the roles of hydration waters during the processes were also discussed. And the adsorption difference between BMP-2and BMP-7on PLA substrate was furtherly explored. The major contributions of this work were as follows:(1) The x-90、x-270、y-90orientations of BMP-7were preferable adsorbed on PLA substrate, and the interaction energy between the y-90orientation and PLA was the most favorable. The VDW interaction between PLA and BMP-7played a dominant role during the adsorption process. The hydration layers on PLA substrate interface were adverse to the protein adsorption. The protein desorption was determined by the interaction between residue and PLA, the smaller interaction, the more difficult to desorb. In addition, the desorption would also be influenced by the interaction between residues.(2) The interactions between BMP-7and PLA and its copolymer were quite different,andthe interaction order is:PLA-co-PCL>PLA-co-PVA>PLA-co-PEG, and BMP-7was only adsorbed on the substrate of PLA-co-PCL. The adsorption behavior of BMP-7would be weaken with the hydrophilic of copolymer increasing. Due to the different oxygen atoms in the system, the structure of hydration layer would be affected. When the hydrophilic of copolymer increaseed, the hydration layer at interface became more order and highly structured, and the thickeness of hydration layer would be increased, which made the adsorption more difficult.(3) The conformation of BMP-2is quite similar to the BMP-7, but the adsorption behavior of these two systems was quite different from each other. For BMP-7systems, the y-90orientation was only adsorbed on PLA preferably, while for BMP-2systems, the most preferable orientation is x-180, which suggested the specificity of BMP-2on PLA Substrates. This difference may be caused by the different number of residues with charge and polarity which faced to the PLA substrate. During the simulation, it was found that the conformation change of BMP-2was slightly larger than that for BMP-7, which may be caused by the different conformation change areas in proteins. For BMP-2system, the conformation change was mainly caused by the residues locating on C-terminal patch. As to BMP-7, it was caused by its loop area. |
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