Clustering molecular dynamics conformations of the CC'-loop of the PD-1 immuno-checkpoint receptor.

Autor: Schreiner W; Medical University of Vienna, Center for Medical Data Science, Spitalgasse 23, A-1090, Vienna, Austria., Karch R; Medical University of Vienna, Center for Medical Data Science, Spitalgasse 23, A-1090, Vienna, Austria., Cibena M; Medical University of Vienna, Center for Medical Data Science, Spitalgasse 23, A-1090, Vienna, Austria., Tomasiak L; Medical University of Vienna, Center for Medical Data Science, Spitalgasse 23, A-1090, Vienna, Austria., Kenn M; Medical University of Vienna, Center for Medical Data Science, Spitalgasse 23, A-1090, Vienna, Austria., Pfeiler G; Medical University of Vienna, Department of Obstetrics and Gynecology, Division of General Gynecology and Gynecologic Oncology, Währinger Gürtel 18-20, A-1090, Vienna, Austria.
Jazyk: angličtina
Zdroj: Computational and structural biotechnology journal [Comput Struct Biotechnol J] 2023 Jul 13; Vol. 21, pp. 3920-3932. Date of Electronic Publication: 2023 Jul 13 (Print Publication: 2023).
DOI: 10.1016/j.csbj.2023.07.004
Abstrakt: Molecular mechanisms within the checkpoint receptor PD-1 are essential for its activation by PD-L1 as well as for blocking such an activation via checkpoint inhibitors. We use molecular dynamics to scrutinize patterns of atomic motion in PD-1 without a ligand. Molecular dynamics is performed for the whole extracellular domain of PD-1, and the analysis focuses on its CC'-loop and some adjacent C α -atoms. We extend previous work by applying common nearest neighbor clustering (Cnn) and compare the performance of this method with Daura clustering as well as UMAP dimension reduction and subsequent agglomerative linkage clustering. As compared to Daura clustering, we found Cnn less sensitive to cutoff selection and better able to return representative clusters for sets of different 3D atomic conformations. Interestingly, Cnn yields results quite similar to UMAP plus linkage clustering.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(© 2023 The Authors.)
Databáze: MEDLINE
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