Because of its governing role in implant biocompatibility, the understanding and control of protein adsorption to implant surfaces continues to be one of the major areas of research in the field of biomaterials. Although greatly desired, a detailed molecular-level understanding of how protein adsorption occurs, and how to control it, are still lacking. Molecular simulation offers great potential to help address these limitations by providing a tool to accurately predict and visualize molecular-level behavior. However, before this potential can be realized, methods must be specifically developed for this application. The overall objective of the proposed R01 research program is therefore to develop molecular simulation capabilities to accurately simulate protein adsorption on surfaces, initially with polymer-like functionality . This will be accomplished by first modifying the well-established CHARMM molecular simulation program to enable two different force fields (either Class I or II type) to be used in the same simulation to separately represent the solution phase and the solid phase. This will enable both phases of an adsorption system to be accurately modeled by a force field that has been specifically developed and validated for that particular material system (e.g., protein in aqueous solution vs. a crystalline polymer). The interface between the two phases, however, must be separately tuned and validated. To accomplish this, experimental adsorption studies using surface plasmon resonance spectroscopy will be conducted using a designed host-guest peptide system to generate experimental adsorption data that will be used to evaluate, tune, and validate a CHARMM interfacial force field for the accurate simulation of protein adsorption behavior at the solid-solution interface. Once validated, the hybrid force field system will be applied to simulate the adsorption behavior for a biomedically relevant protein on functionalized surfaces and the results will be quantitatively compared with a matched set of experimental studies to demonstrate the developed capabilities to accurately simulate protein adsorption behavior. The successful development of these simulation capabilities will provide the foundations for the establishment of molecular simulation as a valuable tool for the biomaterials community for surface design to study and control protein adsorption behavior at the molecular level, with direct applications for medical device design to enhance implant biocompatibility for improved patient care.
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