471002 Molecular Modeling of Antibody-Antigen Binding Near Solid Surfaces

Thursday, November 17, 2016: 2:24 PM
Yosemite C (Hilton San Francisco Union Square)
Derek B. Bush and Thomas A. Knotts IV, Chemical Engineering, Brigham Young University, Provo, UT

Antibody microarrays are a class of biosensors that have the potential to revolutionize scientific research, medical testing, and national defense. This is because they have the potential to screen for thousands of molecules in a parallel, rapid, inexpensive, and easy-to-use manner. However, current antibody microarrays are not widely used due to reliability problems resulting from production tolerances, signal detection, and target selection.

A notable issue with antibody microarrays is that the antibody must perform its function in an environment significantly different than that found in vivo. Prior work in the area focused mainly on the stability of antibodies on a surface and not its affinity for the antigen. It has been shown that antibodies attached to a hydrophobic surface suffer undesirable structural changes due to excessive attraction between the antibody and the surface, but these interactions can be mitigated by using a hydrophilic surface. To move the work forward the nature of antibody-antigen interactions near solid surfaces now needs to be investigated. Our current work aims to improve our understanding of these protein-protein-surface interactions.

Because laboratory methods for studying protein structure either do not provide sufficient detail or are not transferable to heterogeneous environments, molecular simulation can be advantageous for studying surface-bound proteins. However, atomistic models suffer from insufficient sampling that cannot capture protein folding or binding events. Our group uses a recently-developed, coarse-grain, protein-surface model that provides accurate protein folding mechanisms and quantitatively reproduces protein adsorption energies. The simplicity of this model makes it possible to obtain reliable thermodynamic data about large systems of interest.

In this presentation we describe our studies of antibodies and antibody fragments interacting with different antigens near hydrophobic or hydrophilic surfaces. Thermodynamic results will show that the attachment geometry of the affinity molecule relative to the surface can affect antigen binding mechanisms and binding strength. Lysozyme will be used as a model antigen, but additional work using hemagglutinin will demonstrate how antigen size factors into the antigen-binding process near surfaces. The results provide an unprecedented view of the protein-surface and protein-protein interactions crucial to the function of antibody microarrays and offer hope that the rational design of improved microarray technologies is possible.


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