A molecular modeling study of the effect of surface chemistry on the adsorption of a fibronectin fragment spanning the 7-10th type III repeats

Although it is well documented that proteins adsorb onto biomaterial surfaces, relatively little is quantitatively understood about the effects of adsorption on protein orientation and conformation. Because this is the primary determining factor of protein bioactivity, the ability to accurately predict a protein's orientation and conformation following adsorption will be essential for the rational design of biomaterial surfaces to control biological responses. Force field‐based computational chemistry methods provide an excellent means to theoretically address this issue, with the nontrivial requirement that the force field must be tailored to appropriately represent protein adsorption behavior. Accordingly, we have modified an existing force field (CHARMm) based on semiempirical quantum‐mechanical peptide adsorption data to enable it to simulate protein adsorption behavior in an implicit aqueous environment. This modified force field was then applied to predict the adsorption behavior of the 7–10 type III repeats of fibronectin on functionalized surfaces. Predicted changes in adsorption energy and adsorption‐induced conformation as a function of surface chemistry were found to correlate well with experimentally observed trends for these same systems. This work represents a first attempt towards the development of a molecular mechanics force field that is specifically parameterized to accurately simulate protein adsorption to biomaterial surfaces. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 686–698, 2004