The full p53 tetramer-DNA complex is shown in ribbon/cartoon view. Protein chains are tinted separately, DNA is shown in distinct tints, Zn ions are green spheres, and the queried residue is highlighted as magenta spheres on all four p53 chains.
These values come from tetramer-aware computational mutational scanning of the p53 tetramer-DNA complex (PDB 3TS8), in which the same amino-acid substitution was introduced simultaneously into all four symmetry-related p53 chains. MOE was used to estimate predicted changes in intrinsic p53 stability (ΔStability) and DNA-binding affinity (ΔAffinity). Three independent replicate runs were averaged for downstream analysis. Additional methodological details can be found in the manuscript.
Only deleterious-direction effects were propagated into scoring: positive ΔStability was interpreted as destabilization, positive ΔAffinity as reduced DNA binding, and negative values were set to zero for normalization and classification. Tetrameric effects were normalized as Zstab = max(0, ΔStability)/dstab and Zaff = max(0, ΔAffinity)/daff, where dstab and daff are the global standard deviations of the corresponding non-negative effects across the scan.
For spreadsheet-style interpretation, stability effects were grouped as none, weak, moderate, or strong based on Zstab, and affinity-reduction effects were similarly grouped using Zaff. Mechanistic classes were then assigned using empirically derived thresholds from the positive Z-score distributions; in the tetramer-DNA scan, the current dataset used Zstab > 1.832 for Zn-associated destabilization, Zstab > 2.655 for strong destabilization, and Zaff > 0.558 for substantial affinity impairment. Rescue prioritization was stability-led, with Zn-disrupting and strongly destabilizing variants prioritized most highly.