Molecular Dynamics Simulation Of The Interaction Of A Hydrophilic Structurally Modified Polyurethane Material With The Calcium-binding EGF-like Domain Of The Factor FIX

The interaction between blood and the surface of bio-medical material directly influence the blood compatibility of the material.But the mechanism of this interaction is poorly understood yet because of its complicacy.Nowadays,biomedical materials research develops so quickly.However,the experimental evaluation for material's biocompatibility can only provide us with specific results,and it can't explain the clotting mechanism on the molecular level.As the most direct method of theoretically investigating the behaviors of complex molecular systems,molecular modeling is very suitable for the simulation and explanation of the protein-surface interactions.According to the theory of Maintain Natural Behavior,the surface structure of anti-thromobogenic materials should maintain the natural behavior of the haemproteins or hemocytes,i.e.,their natural superior conformations and their natural way of conformation transformation.So we use the molecular modeling software,Discovery Studio(DS),for the following research.We choose the cbEGF-like domain of coagulation factor IX as research objects to simulate the interaction between blood protein and different hydrophilic surfaces.The theoretical blood compatibility of the surfaces is evaluated.And the effect of surfacial structure on the blood compatibility of materials is dicussed:(1)We choose two anionic hydrophilic structures,2-[(2-aminoethyl)amino]-ethanesulfonic acid monosodium salt(AAS)and 3-sulfopropyl acrylate potassium salt(SPAPS)to modify polyurethane surface,then similate the interactions between modified polyurethane surface and the cbEGF-like domain.The results show that the modified surface can well maintain the natural state of the cbEGF-like domain.And the theoretical blood compatibility of the polyurethane modified by anionic hydrophilic structures is better with higher grafting rate.We also find that the length of grafting chain and the the theoretical blood compatibility of the polyurethane keep the corresponding increasing relationship.(2)(2-(acryloyoxy)ethyl)trimethylammonium chloride(DAC)and diethyldiallylammonium chloride(DEDAAC)have been choosen as two cationic hydrophilic structures to modify polyurethane surface.We use DS to similate the interactions between modified polyurethane surfaces and the cbEGF-like domain.The results show that the the polyurethane modified by cationic hydrophilic structures can rarely maintain the cbEGF-like domain's natural state well.Only when the grafting rate is very small,the theoretical blood compatibility of the material surface is well.We also find that the length of grafting chain and the the theoretical blood compatibility of the polyurethane keep the corresponding decreasing relationship.(3)3-dimethyl(methacryloyloxyethyl)ammonium propane sulfonate(DMAPS)and N,N'-dimethyl-N-(4-vinylbenzyl)-N-(3-sulfopropyl)-ammonium(DMVSA)have been chosen as two zwitterionic hydrophilic structures to modify polyurethane surface.Then simulations of the interactions between modified polyurethane surface and the cbEGF-like domain are carried out by DS.The results show that the polyurethane modified by zwitterionic hydrophilic structures can maintain the cbEGF-like domain's natural state very well.And the surface can maintain the the cbEGF-like domain's natural state better with higher grafting rate.We also find that the length of grafting chain and the the theoretical blood compatibility of the polyurethane keep the corresponding increasing relationship.The research provides the details of the protein-surface interactions on molecular level,and shows the change of the protein(segment)conformation caused by different surface.Molecular modeling provides us with a probe into protein-surface interaction,through gathering the information about the modeling systems in molecular level we can analyze the anti-clotting mechanism of biomaterials,and it has important significance for the further research.