Spatial and Sequential Topological Analysis of Molecular Dynamics Simulations of IgG1 Fc Domains

Published

April 22, 2025

Author(s)

Melinda Kleczynski, Christina Bergonzo, Anthony Kearsley

Abstract

Monoclonal antibodies are utilized in a wide range of biomedical applications. The NIST Monoclonal Antibody is a resource for developing analysis methods for monoclonal antibody based biopharmaceutical platforms. Techniques from topological data analysis quantify structural features such as loops and tunnels which are not easily measured by classical data analysis methods. In this paper, we introduce the Gaussian CROCKER Column Differences (GCCD) matrix, which augments standard topological data analysis summaries with biological sequence information. We use GCCD matrices to successfully differentiate between glycosylated and aglycosylated conformations from molecular dynamics simulations of the NIST Monoclonal Antibody Fc domain. We are optimistic that other researchers will be able to utilize GCCD matrices to quantify multiscale spatial and sequential features.

Citation

Journal of Chemical Theory and Computation

Volume

21

Issue

9

Pub Type

Journals

Download Paper

https://doi.org/10.1021/acs.jctc.5c00161

Local Download

Keywords

Topological data analysis, Molecular dynamics simulations, Monoclonal antibodies

Citation

Kleczynski, M. , Bergonzo, C. and Kearsley, A. (2025), Spatial and Sequential Topological Analysis of Molecular Dynamics Simulations of IgG1 Fc Domains, Journal of Chemical Theory and Computation, [online], https://doi.org/10.1021/acs.jctc.5c00161, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=959236 (Accessed October 11, 2025)