Keywords

Molecular simulations, Folding pathways, Enthalpy, Thermodynamic properties, Microarrays, Denaturation (biochemistry), Antibody, Protein structure, Immune system, Statistical analysis

Abstract

Despite their potential benefits, antibody microarrays have fallen short of performing reliably and have not found widespread use outside of the research setting. Experimental techniques have been unable to determine what is occurring on the surface of an atomic level, so molecular simulation has emerged as the primary method of investigating protein/surface interactions. Simulations of small proteins have indicated that the stability of the protein is a function of the residue on the protein where a tether is placed. The purpose of this research is to see whether these findings also apply to antibodies, with their greater size and complexity. To determine this, 24 tethering locations were selected on the antibody Protein Data Bank (PDB) ID: 1IGT. Replica exchange simulations were run on two different surfaces, one hydrophobic and one hydrophilic, to determine the degree to which these tethering sites stabilize or destabilize the antibody. Results showed that antibodies tethered to hydrophobic surfaces were in general less stable than antibodies tethered to hydrophilic surfaces. Moreover, the stability of the antibody was a function of the tether location on hydrophobic surfaces but not hydrophilic surfaces.

Original Publication Citation

R. W. Grawe and T. A. Knotts IV, The Effects of Tether Placement on Antibody Stability on Surfaces, J. Chem. Phys., 146, 215102 (2017). (Cover Article, 2017 Editor's Choice Award)