KRAS R68G继发突变引发KRASG12D靶向抑制剂MRTX1133耐药的机制研究

王高明, 崔然, 黎彦璟, 刘颖斌

Study on the mechanism of KRAS R68G secondary mutation-induced resistance to KRASG12D-targeted inhibitor MRTX1133

WANG Gaoming, CUI Ran, LI Yanjing, LIU Yingbin

图6 Switch Ⅰ和Switch Ⅱ区域在运动中的关系 Note： A. DCCM plot of the KRASG12D system. B. Delta DCCM plot of the KRASG12D/R68G system relative to the KRASG12D system. Region a represents the decoupled motion between Switch Ⅰ and P-loop; region b indicates the decoupled motion between Switch Ⅱ and P-loop; region c suggests the decoupled motion between Switch Ⅰ and Switch Ⅱ. C. Distance distribution of Cα atoms between P34 and G60 (dP34-G60). D. Average hydrogen bonds formed between Switch Ⅰ and Switch Ⅱ during the simulations. E. Representative structures of KRASG12D (magenta) and KRASG12D/R68G (cyan) systems show the distance (yellow dotted line) and polar contacts (green dotted line) between Switch Ⅰ and Switch Ⅱ.

Fig 6 Dynamic relationship between Switch Ⅰ and Switch Ⅱ regions