Estimation of Dissociation Constant of ARS-1620 Complex with KRASG12C Protein by Molecular Modeling

Abstract

The paper presents the results of the estimation of the KRASG12C ⋅ GDP ⋅ ARS-1620 complex dissociation constant. The ARS-1620 is a potential inhibitor of the cellular signal transduction of the KRAS enzyme with the oncogenic G12C mutation. The value of the dissociation constant estimated by molecular docking is 280 nM and 0.3 ± 0.1 nM within the molecular dynamics combined with the Hamiltonian replica exchange umbrella sampling approach.