Systematic cysteine scanning identifies a druggable pocket in oncogenic KRAS

We developed Cysteine Mapping of Accessible Pockets (CysMAP), a method for identifying druggable pockets in proteins. CysMAP employs systematic pooled cysteine variant libraries screened against diverse covalent compound libraries by intact LC-MS. Here, we applied CysMAP to 189 KRAS(G12D) variants, purifying KRAS Cys-variants and screening them against 47 covalent compounds, quantifying accessibility and reactivity across KRAS(G12D).