Appendices and Supplementary Material

A.1 Equations for Conformational Energy Landscape Overlap Analysis To quantify the similarity between the protein conformations generated by AI-based models and those in the ProteinConformers dataset, the following three commonly used overlap metrics are employed: Interaction overlap, coverage, and the Jaccard index. These metrics evaluate the extent of agreement in low-energy regions between the protein conformers from different models of the same protein, based on a specified energy threshold. Let A = {Ai,j} and B = {Bi,j} where i,j [0,N], denote the two-dimensional free energy landscapes corresponding of two conformational ensembles. Each element Ai,j and Bi,j represents the free energy value at a specific grid point in the conformational energy landscape. For a given energy threshold τ (e.g., 40 kJ/mol), the number of shared low-energy conformations is defined as: |A B| = Figure 6: Comparison of conformational landscapes for protein T1030, generated by ProteinConformers and protein conformation generative models.