Chapter 11
The Allosteric Effect in Antibody-Antigen Recognition
Jun Zhao, Ruth Nussinov, and Buyong Ma
Abstract
We studied the molecular details of the recognition of antigens by the variable domain of their cognate
antibodies in as well as those elicited by the constant domains, which do not directly interact with antigens.
Such effects are difficult to study experimentally; however, molecular dynamics simulations and subsequent
residue interaction network analysis provide insight into the allosteric communication between the antigenbinding CDR region and the constant domain. We performed MD simulations of the complex of Fab and
prion-associated peptide in the apo and bound forms and follow the conformational changes in the
antibody and cross-talk between its subunits and with antigens. These protocols could be generally applied
for studies of other antigens-antibody recognition systems.
Key words Antibody-antigen interaction, Motion correlation, Dynamic network, Community analysis, Disulfide bond, Allosteric effect
1 Introduction
Protein conformational dynamics and fluctuations in water are
intrinsic thermodynamic phenomena, with the distributions of
the states on the energy landscape determined by statistical thermodynamics. Protein dynamics and conformational changes have
been optimized by evolution to perform biological functions
[1]. Proteins are intrinsically allosteric, and their residue interaction
networks are controlled by the protein energy landscape [2–6].
The antibody variable regions are necessarily flexible to enable
recognition of diversified targets. Recognition is associated with
structural transitions [7–9]. The variable domains, especially
CDRs, mainly control the specificity and affinity [10], while the
constant domains modulate the isotype/effector [11] and independently the variable and constant domains functions. Recent studies
indicate that besides the variable domains, the constant domain also
plays an essential role in antigen binding [12–16]. There is direct
communication between the variable domains of the light and
heavy chains [17] and distant communication between the variable
Luisa Di Paola and Alessandro Giuliani (eds.), Allostery: Methods and Protocols, Methods in Molecular Biology, vol. 2253,
https://doi.org/10.1007/978-1-0716-1154-8_11, © Springer Science+Business Media, LLC, part of Springer Nature 2021
175
The Allosteric Effect in Antibody-Antigen Recognition
Jun Zhao, Ruth Nussinov, and Buyong Ma
Abstract
We studied the molecular details of the recognition of antigens by the variable domain of their cognate
antibodies in as well as those elicited by the constant domains, which do not directly interact with antigens.
Such effects are difficult to study experimentally; however, molecular dynamics simulations and subsequent
residue interaction network analysis provide insight into the allosteric communication between the antigenbinding CDR region and the constant domain. We performed MD simulations of the complex of Fab and
prion-associated peptide in the apo and bound forms and follow the conformational changes in the
antibody and cross-talk between its subunits and with antigens. These protocols could be generally applied
for studies of other antigens-antibody recognition systems.
Key words Antibody-antigen interaction, Motion correlation, Dynamic network, Community analysis, Disulfide bond, Allosteric effect
1 Introduction
Protein conformational dynamics and fluctuations in water are
intrinsic thermodynamic phenomena, with the distributions of
the states on the energy landscape determined by statistical thermodynamics. Protein dynamics and conformational changes have
been optimized by evolution to perform biological functions
[1]. Proteins are intrinsically allosteric, and their residue interaction
networks are controlled by the protein energy landscape [2–6].
The antibody variable regions are necessarily flexible to enable
recognition of diversified targets. Recognition is associated with
structural transitions [7–9]. The variable domains, especially
CDRs, mainly control the specificity and affinity [10], while the
constant domains modulate the isotype/effector [11] and independently the variable and constant domains functions. Recent studies
indicate that besides the variable domains, the constant domain also
plays an essential role in antigen binding [12–16]. There is direct
communication between the variable domains of the light and
heavy chains [17] and distant communication between the variable
Luisa Di Paola and Alessandro Giuliani (eds.), Allostery: Methods and Protocols, Methods in Molecular Biology, vol. 2253,
https://doi.org/10.1007/978-1-0716-1154-8_11, © Springer Science+Business Media, LLC, part of Springer Nature 2021
175