New insights into the microscopic interactions associated with the physical mechanism of action of highly diluted biologics

July 6, 2021

Title

New insights into the microscopic interactions associated with the physical mechanism of action of highly diluted biologics

Author

Kristina N. Woods

Year

2021

Journal

Scientific reports

Abstract

In this investigation, we report the effect on the microscopic dynamics and interactions of the cytokine interferon gamma (IFN-γ) and antibodies to IFN-γ (anti-IFN-γ) and to the interferon gamma receptor 1 (anti-IFNGR1) prepared in exceptionally dilute solutions of initial proteins. Using both THz spectroscopy and molecular dynamics simulations we have uncovered that the high dilution method of sample preparation results in the reorganization of the sample surface residue dynamics at the solvent–protein interface that leads to both structural and kinetic heterogeneous dynamics that ultimately create interactions that enhance the binding probability of the antigen binding site. Our results indicate that the modified interfacial dynamics of anti-IFN-γ and anti-IFGNR1 that we probe experimentally are directly associated with alterations in the complementarity regions of the distinct antibodies that designate both antigen–antibody affinity and recognition.

Instrument

FT/IR-6000

Keywords

microscopic, dynamics, interaction, antibody, affinity