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Fig. 2 | BMC Bioinformatics

Fig. 2

From: Molecular dynamics of the immune checkpoint programmed cell death protein I, PD-1: conformational changes of the BC-loop upon binding of the ligand PD-L1 and the monoclonal antibody nivolumab

Fig. 2

PD-L1 induces a unique BC-loop conformation. The clustering algorithm as described by Daura et al. [20] was applied (a). Colors denote the origin of the structures. Only the first 25 clusters are shown. PD-1PD-L1 (red) and PD-1Niv (blue) exhibit for 25 and 60% of the time, respectively the same conformation. Over 90% of the structures of PD-1Apo (black) are distributed between cluster 2 and 7. Cluster 3 and 5 contain only PD-1PD-L1 structures whereas cluster 4 consist primarily PD-1Niv structures. The number of structures is equivalent to the time the BC-loop resided in a certain conformation. b The distance map generated with multidimensional scaling [21] shows the relationship between the conformations found with the Daura et al. [20] clustering algorithm. Clusters with similar structures are in proximity. Three areas are distinguishable (circled by hand) which are named meta-cluster I, II and III. Meta-cluster I is occupied by the PD-1Apo, PD-1PD-L1 and PD-1Niv. Meta-cluster II consists of clusters formed by PD-1Apo. Meta-cluster III consists only of structures of PD-1PD-L1. This demonstrates a clear shift of the BC-loop conformation in the Nivolumab complex. The colors represent the origins of the central frames. c Superimposed crystal structures of the central frames of the first five clusters visualized with VMD 1.9.3. Structures of clusters 1, 4 and 5 exhibit a similar BC-loop conformation. Cluster 2 and 3 exhibit distinct BC-loop conformations. BC-loop is colored; other domains are shown in grey. PD-1Apo structure is shown in cyan instead of black

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