AVS 49th International Symposium
    Biomaterials Monday Sessions
       Session BI+VT-MoA

Paper BI+VT-MoA5
Prediction of Adsorption Behavior of Fibronectin as a Function of Surface Functionality Using a Customized Protein Adsorption Force-Field

Monday, November 4, 2002, 3:20 pm, Room C-201

Session: Protein Surface Interactions
Presenter: R.A. Latour, Clemson University
Authors: R.A. Latour, Clemson University
K.A. Wilson, Clemson University
A.J. Garcia, Georgia Institute of Technology
S.J. Stuart, Clemson University
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The ability of a cell to bind to an adsorbed protein layer on a biomaterial surface is dependent on the structure and availability of the protein's cell binding domains following adsorption. A well-known example of this is integrin binding to the PHSRN and RGD sites located on the 9th & 10th type III repeats of fibronectin (Fn). The objective of this research was to utilize computational chemistry to predict the relative orientation and accessibility of these cell-binding domains in Fn after adsorption as a function of surface functionality (CH3, OH, NH3+, COO-). Modeling was conducted using an SGI O2/Onyx computational system with InsightII software (Accelrys). The Charmm force-field was used to simulate intramolecular interactions for the fibronectin, while a new set of force-field parameters was created to simulate the interactions between the fibronectin and the surface. The new force-field parameters were set to provide similar energy vs. surface separation plots for peptide residue-surface adsorption as determined by previous semi-empirical modeling studies using MOPAC/PM3/COSMO. Initial energy vs Fn orientation maps were generated followed by 50 ps molecular dynamics simulations at selected positions to assess initial adsorbed Fn behavior. Results suggest that the CH3 and COO- surfaces should most strongly inhibit integrin binding, but by different mechanisms; the CH3 surface by disrupting Fn structure and the COO- surface by blocking accessibility. The OH and NH3 surfaces were predicted to preserve binding site structure and accessibility. Results compare favorably with experimental studies and provide likely molecular mechanisms that help explain experimentally observed behavior.