# LEGENDS.md — fig1_kras_landscape

## Figure 1 | Conformational plasticity and binder interaction landscape of KRAS

**a**, Structural overlay of KRAS G12C ON and OFF switch states (headless PyMOL
ray-traced render; probe-pass anchors from `render_anchors.json`). Vector labels
mark the KRAS core (right anchor) and the Switch-II lobe with its covalent
inhibitor AMG 510 / sotorasib (left anchor). Opaque soft-gray receptor surface
with two-sided lighting and +18° cavity tilt; no in-scene bitmap text.

**b**, Per-residue Cα displacement (Å) between the two switch states across
residues 1–169 (chain A, `conformer_rmsf.tsv`). Shaded bands mark the Switch-I
(residues 30–38) and Switch-II (residues 60–69) regions. Peak callouts are
placed at algorithmic windowed maxima (Asp33 = 3.25 Å in Switch-I; Glu63 =
4.12 Å in Switch-II). The dashed line marks the sequence mean (0.62 Å),
integrated into the y-axis as a two-line tick label to avoid in-plot box
collisions.

**c**, Binder–residue interaction hotspot matrix (`binder_hotspot_matrix.tsv`).
Cell shade encodes buried surface area (BSA) per receptor residue (Ų, Blues
scale, horizontal colorbar below). Black dots mark hydrogen bonds and blue
triangles mark salt bridges (glyph legend below panel). Columns are grouped by
consensus site — Switch-I (Y32), Switch-II (G60, Q61, E62, Y64), Pocket (H95,
Y96, Q99), and Core (V9, G12) — with site chips above and vertical partition
dividers; residue headers use staggered baselines. Rows: Sotorasib, Adagrasib,
BI-2852, MRTX-1133, Monobody NS1.

**d**, Total interface BSA (Ų) per binder, stacked by receptor subunit
(`binder_summary_data.tsv`): dark segments = primary (chain A) contribution,
light segments = secondary/scaffold contribution (Monobody NS1 only, 135.2 Ų).
Stack totals equal the exact sum of partitioned chain values (asserted at
generation time). Bar colors encode binder modality (blue, small molecule;
green, protein binder; legend inside panel). Row order is synchronized with the
heatmap in **c** (top-to-bottom).

### Data provenance

| Binder | Modality | Target site | PDB entry |
| --- | --- | --- | --- |
| Sotorasib (AMG 510) | Small molecule | Switch-II | 6OIM |
| Adagrasib (MRTX-849) | Small molecule | Switch-II | 6USZ |
| BI-2852 | Small molecule | Switch-I | 6GJ8 |
| MRTX-1133 | Small molecule | Switch-II | 7RPZ |
| Monobody NS1 | Protein | Allosteric | 5V6V |

### QA certification (three-layer pipeline)

| Gate | Result |
| --- | --- |
| Layer 1 — static preflight (sans-serif, 7 pt base, `pdf.fonttype=42`, `svg.fonttype='none'`) | PASS |
| Layer 2 — `audit_panel_alignment.py` (≤ 1.5 pt, 4 comparisons) | PASS — 0 fail, 0 warn (`fig1_kras_landscape.alignment.json`) |
| Layer 2 — `audit_figure_collisions.py` (0 FAIL required) | PASS — 0 fail, 0 warn (`fig1_kras_landscape.collision-audit.json`) |
| Layer 2 — `audit_pdf_text.py` (≥ 5.0 pt glyph floor) | PASS — minimum found 5.2 pt, 0 runs below |
| Layer 3 — vision-model semantic review | PASS — panel a labels legible and frame-contained; panel c/d row order synchronized; Switch-I/Switch-II bands labeled |

### Files

- `fig1_kras_landscape.pdf` — vector (submission)
- `fig1_kras_landscape.svg` — editable vector
- `fig1_kras_landscape.png` — 300 dpi raster
- `fig1_kras_landscape.py` — deterministic generation script (uv env: `../../.venv/bin/python`)
- `data/` — declarative input contracts (TSV/JSON/PNG) copied from `../../data/`