Investigating Allostery in Molecular Recognition: Insights from a Computational Study of Multiple Antibody–Antigen Complexes

Antibody–antigen recognition plays a key role
in the immune
response against pathogens. Here, we have investigated various aspects
of this problem by analyzing a large and diverse set of antibodies
and their respective complexes with protein antigens through atomistic
simulations. Common features of antibody response to the presence
of antigens are elucidated by the analysis of the proteins’
internal dynamics and coordination in different ligand states, combined
with the analysis of the interaction networks implicated in the stabilization
of functional structures. The use of a common structural reference
reveals preferential changes in the dynamic coordination and intramolecular
interaction networks induced by antigen binding and shared by all
antibodies. Such changes propagate from the binding region through
the whole immunoglobulin domains. Overall, complexed antibodies show
more diffuse networks of nonbonded interactions and a general higher
internal dynamic coordination, which preferentially involve the immunoglobulin
(Ig) domains of the heavy chain. The combined results provide atomistic
insights into the correlations between the modulation of conformational
dynamics, structural stability, and allosteric signal transduction.
In particular, the results suggest that specific networks of residues,
shared among all the analyzed proteins, define the molecular pathways
by which antibody structures respond to antigen binding. Our studies
may have implications in practical use, such as the rational design
of antibodies with specifically modulated antigen-binding affinities.