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

Corrada, D., Morra, G., Colombo, G. (2013). Investigating allostery in molecular recognition: insights from a computational study of multiple antibody-antigen complexes. JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL, 117(2), 535-552 [10.1021/jp310753z].

Investigating allostery in molecular recognition: insights from a computational study of multiple antibody-antigen complexes

CORRADA, DARIO;
2013

Abstract

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
Articolo in rivista - Articolo scientifico
Animals; Antibodies; Antigens; Mice; Molecular Dynamics Simulation; Protein Structure, Tertiary; Antigen-Antibody Complex
English
535
552
18
Corrada, D., Morra, G., Colombo, G. (2013). Investigating allostery in molecular recognition: insights from a computational study of multiple antibody-antigen complexes. JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL, 117(2), 535-552 [10.1021/jp310753z].
Corrada, D; Morra, G; Colombo, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/48628
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