Antigen Binding Reshapes Antibody Energy Landscape and Conformation Dynamics

Kazi Lutful Kabir, Ruth Nussinov, Buyong Ma, Amarda Shehu

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

1 Scopus citations

Abstract

This study elucidates the conformation dynamics of the free and antigen-bound antibody. Previous work has verified that antigen binding allosterically promotes Fc receptor recognition. Analysis of extensive molecular dynamics simulations finds that the energy landscape may play a decisive role in coordinating conformation changes but does not provide connections between the various conformational states. Here we provide such a connection. To obtain a detailed understanding of the impact of antigen binding on antibody conformation dynamics, this study utilizes Markov State Models to summarize the conformation dynamics probed in silico. We additionally equip these models with the ability to directly exploit the energy landscape view of dynamics via a computational method that detects energy basins and so allows utilizing detected basins as macrostates for the Markov State Model. Our study reveals many interesting findings and suggests that the antigen-bound form with high energy may provide many dynamic processes to further enhance co-factor binding of the antibody in the next step.

Original languageEnglish
Title of host publicationProceedings - 2021 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2021
EditorsYufei Huang, Lukasz Kurgan, Feng Luo, Xiaohua Tony Hu, Yidong Chen, Edward Dougherty, Andrzej Kloczkowski, Yaohang Li
PublisherInstitute of Electrical and Electronics Engineers Inc.
Pages2519-2526
Number of pages8
ISBN (Electronic)9781665401265
DOIs
StatePublished - 2021
Externally publishedYes
Event2021 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2021 - Virtual, Online, United States
Duration: 9 Dec 202112 Dec 2021

Publication series

NameProceedings - 2021 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2021

Conference

Conference2021 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2021
Country/TerritoryUnited States
CityVirtual, Online
Period9/12/2112/12/21

Funding

FundersFunder number
National Science Foundation1900061
National Institutes of HealthHHSN261201500003I
National Cancer Institute
NIH Clinical Center

    Keywords

    • Antibody
    • Basin
    • Conformation
    • Energy landscape
    • Markov state model
    • Molecular dynamics

    Fingerprint

    Dive into the research topics of 'Antigen Binding Reshapes Antibody Energy Landscape and Conformation Dynamics'. Together they form a unique fingerprint.

    Cite this