Adsorption-desorption Mechanism Of Proteins On Hydroxyapatite

With the development of medicinal science,material science and biotechnology, the adsorption behaviors of proteins onto hydroxyapatite(HAP)surfaces have received much attention due to its importance on the control of interfacial behavior of biomacromolecule and the design of biomedical materials.In this paper,the adsorption-desorption dynamical behaviors of proteins on HAP surfaces and the interaction mechanism were studied systematically through the molecular dynamics (MD)simulation and the quantum mechanics calculation.And then the differences between four types of proteins were compared in order to find some universal phenomena.It is showed that the regulation of the interaction between proteins and the HAP via the control on the atomic level is possible in the future.This paper is mainly composed of the following six parts:Chapter 1:The background and meanings of this thesis were introduced,as well as a brief review of this issue.Chapter 2:The methods of molecular dynamics simulation and the quantum mechanics calculation were introduced.Chapter 3:The adsorption-desorption dynamics of BMP-2 on HAP(001)surface were studied in detail.Three types of adsorption functional groups,-OH,-NH₂,and -COO^-,are found for protein BMP-2 to interact with HAP(001)surface.As active groups,they are usually neighboring with strongly electron-attracting groups directly, such as -C=O.According to the different interfaces proteins encountered with HAP crystallite,there might be one or several types of adsorption groups working simultaneously.The adsorption mechanism was explored in detail.In addition to the Coulombic force,which has been widely accepted,the water-bridged H-bond is found to be very important as well.For groups with no net charge,such as -OH and -NH₂,it is the water-bridged H-bond that results in the adsorption.The results of the quantum chemistry calculations confirm that this type of water-bridged H-bond does exist.Chapter 4:The effect of different orientation of BMP-2 was studied.It is found that the orientation of BMP-2 plays an important role on the interaction with HAP surface.The types and the number of adsorptive residues,the intensity of interaction and the adsorption time are various among the six systems.System I exhibits the strongest interaction,and the number of adsorptive residues are the most correspondingly.Therefore,this orientation might be the most preferential one for BMP-2 to interact with the HAP(001)surface.Chapter 5:The effect of different textures of HAP surfaces on the adsorption behavior of BMP-7 was studied.It is observed that the interaction energy curve from SMD simulation can provide the dynamic behavior of BMP-7 in detail.It exhibits not only the relative interaction intensity semiquantitatively,but also the number of desorbed groups,the type of desorbed groups,and the time of desorption.Detailed studies show that the strong interaction might induce dramatic conformational changes in BMP-7.The largest conformational change occurs in system 100+a. According to the different textures of HAP surfaces,there are only two categories of functional groups,that is,-COO^- and -NH₃⁺ or -C(NH₂)₂⁺.The quantum mechanics calculations suggest that there is a phenomenon of electron transfer from HAP to the groups of BMP-7 during the adsorption process.Chapter 6:The dynamics behaviors of four types of proteins,i.e.BMP-2,BMP-7, LRAP and FN-â…¢₁₀were compared.It was showed that there are four types of residues(Asp,Glu,Lys and Arg)which all participated in the adsorption of these four types of proteins onto the HAP.And they should be considered sincerely when talking about the interaction between other proteins and the HAP.The orientation of proteins plays an important role on the interaction.Even though,each type of proteins will have a specific orientation with the most probability.The conformation of proteins probably changed because of the influence of the HAP surface.Generally,the stronger the interaction is,the greater the conformational changes will be,which might therefore influence the bioactivity of the proteins.