| # Application Flowchart | |
| ## Data Pipeline | |
| ```mermaid | |
| flowchart TD | |
| A[Variant list CSV/XLSX] --> B[HGVS parse + NP_000537.3 QC] | |
| B --> C{Mutation class} | |
| C -->|Missense| D[Literature or physics ΔΔG] | |
| C -->|Stop-gain / splice| E[Alternative strategy] | |
| D --> F[Cavity volume + SiteMap-like Dscore] | |
| F -->|Gate open| G[Library + Lipinski/Veber/QED] | |
| F -->|Hold/closed| E | |
| G --> H[Complementarity / Kd→ΔG] | |
| H --> I[Matched WT vs mutant scores] | |
| I --> J[ADMET + occupancy MD proxies] | |
| J --> K["R(c,m) Rescue/Opportunity"] | |
| K --> M[Dashboard + PDF / CSV] | |
| E --> M | |
| U[Optional uploaded dock_mut/dock_wt] --> I | |
| ``` | |
| ## Scoring | |
| ```mermaid | |
| flowchart TD | |
| Kd[Published Kd] -->|ΔG = RT ln Kd| Bmut[Bmut] | |
| Emp[Volume/hydrophobic complementarity] --> Bmut | |
| WT[Matched WT protocol] --> Sel[Selectivity] | |
| Bmut --> R[Rescue / Opportunity Score] | |
| Sel --> R | |
| MD[Occupancy / RMSD / MMGBSA] --> R | |
| Fr[Cavity + mechanism] --> R | |
| AD[Lipinski Veber Egan QED hERG] --> R | |
| Ev[Evidence] --> R | |
| Risk[Liabilities + OOD] --> R | |
| R --> Rec{Go / Hold / No-go} | |
| ``` | |