Effects from metal ion in tumor endothelial marker 8 and anthrax protective antigen: BioLayer Interferometry experiment and molecular dynamics simulation study.

One of the anthrax receptors, tumor endothelial marker 8 (TEM8), is reported to be a potential anticancer target due to its over-expression during tumor angiogenesis. To extend our BioLayer Interferometry study in PA-TEM8 binding, we present a computational approach to reveal the role of an integral metal ion on receptor structure and binding thermodynamics. We estimated the interaction energy between PA and TEM8 using computer simulation. Consistent with experimental study, computational results indicate the metal ion in TEM8 contributes significantly to the binding affinity, and PA-TEM8 binding is more favorable in the presence of Mg2+ than Ca2+ . Further, computational analysis suggests that the differences in PA-TEM8 binding affinity are comparable to the closely related integrin proteins. The conformation change, which linked to changes in activity of integrins, was not found in TEM8. In the present of Mg2+ , TEM8 remains in a conformation analogous to an integrin open (high-affinity) conformation. © 2017 Wiley Periodicals, Inc.