Skip to main content
. 2022 Mar 3;11:e75751. doi: 10.7554/eLife.75751

Figure 3. Distinct conformations can be delineated using principal component analysis (PCA).

(A) Conformational heterogeneity in AlphaFold2 (AF2) models of LAT1. Experimental inward-facing (IF) and outward-facing (OF) conformations shown in teal and orange, respectively, while the gallery of AF2 models generated using 128 sequences are shown in gray. (B) Distribution of AF2 models generated using multiple sequence alignments (MSAs) with 32 or more sequences across the first principal component (PC1) following PCA (gray traces). Scatter plots comparing each model’s position along PC1 and its structural similarity to experimentally determined structures. Teal: similarity to IF (transporters) or inactive (G-protein-coupled receptors, GPCRs) conformation. Orange: similarity to OF (transporters) or active (GPCRs) conformation. Each model is shown twice, once in teal and once in orange. Native structures are shown as black dots.

Figure 3.

Figure 3—figure supplement 1. Models sampled by AlphaFold2 (AF2) in multiple conformations cannot be fully explained by linear interpolation of two end structures.

Figure 3—figure supplement 1.

Principal component analysis (PCA) of AF2 models, with colors corresponding to the depth of the multiple sequence alignments (MSAs) used for prediction. Experimental structures in an inward-facing or inactive state are shown as teal diamonds, while structures in an outward-facing or active state are shown as orange diamonds.
Figure 3—figure supplement 2. Example predictions of the adhesion G-protein-coupled receptor (aGPCR) GPR114/ADGRG5.

Figure 3—figure supplement 2.

Top: kernel density estimate of the first principal component (PC1) following principal component analysis (PCA on all AlphaFold2 (AF2)) models. Bottom: comparison of PC1 and template modeling (TM) score values; alignments were measured from the AF2 database model, which is indicated by the green dot. Right: models extracted from the cluster centers appear to adopt three distinct conformations.