AVS 54th International Symposium
    Biomaterial Interfaces Tuesday Sessions
       Session BI-TuM

Paper BI-TuM5
Development of a Molecular Modeling Program Specifically Designed for the Simulation of Protein Adsorption to Biomaterials Surfaces

Tuesday, October 16, 2007, 9:20 am, Room 609

Session: Proteins at Interfaces
Presenter: R.A. Latour, Clemson University
Authors: R.A. Latour, Clemson University
P. Biswas, Clemson University
B.R. Brooks, Laboratory of Computational Biology - NIH
S.J. Stuart, Clemson University
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Although it is well understood that cellular responses to biomaterial surfaces and substrates for tissue engineering and regenerative medicine are primarily governed by the bioactive state of adsorbed proteins, very little is known regarding the molecular-level events involved in these processes. Without this understanding, surface design can only be approached by trial and error. Molecular simulation provides a means to overcome this problem by providing an approach to directly investigate protein-surface interactions at the molecular level. Molecular simulation methods have already been successfully developed and widely applied for the study of protein folding and for drug design. However, these methods are not suitable for protein-surface interactions studies as it involves solid-liquid multiphase interactions which must be addressed specifically. Also, force-fields specifically designed for solid or liquid phase are not easily transferable. We are therefore working to develop capabilities within the CHARMM molecular simulation program to specifically adapt it for the simulation of protein adsorption processes to biomaterials surfaces. In particular, capabilities are being developed to control the solid phase, the solution phase, and the interactions between them with three separate force fields, thus enabling the molecular behavior of each phase of the system to be accurately represented. While force field parameters for proteins in solution and various solid materials have previously been developed and validated, parameters for the interactions between proteins in solution and functional groups presented by a solid surface have not. As an integral part of this program, we are therefore also generating experimental data on peptide-surface interactions for a wide range of amino acid residues and polymer-like functional groups for the design and validation of an interfacial force field for use in the developed program. In this presentation, we will describe the modifications in the CHARMM code and results exhibiting the usefulness of this hybrid force field approach for the simulation of peptide and protein interactions with a solid surface. Once fully developed, this approach holds promise to provide the biomaterials field with an exciting new tool to proactively design biomaterials surfaces to direct cellular response by controlling the bioactive state of adsorbed proteins with broad application in biomedical engineering and bionanotechnology.