Iskandar Sitdikov, Jennifer Glick, et al.
APS March Meeting 2023
RAS is a signaling protein associated with the cell membrane that is mutated in up to 30% of human cancers. RAS signaling has been proposed to be regulated by dynamic heterogeneity of the cell membrane. Investigating such a mechanism requires near-atomistic detail at macroscopic temporal and spatial scales, which is not possible with conventional computational or experimental techniques. We demonstrate here a multiscale simulation infrastructure that uses machine learning to create a scale-bridging ensemble of over 100,000 simulations of active wild-type KRAS on a complex, asymmetric membrane. Initialized and validated with experimental data (including a new structure of active wild-type KRAS), these simulations represent a substantial advance in the ability to characterize RAS-membrane biology. We report distinctive patterns of local lipid composition that correlate with interfacially promiscuous RAS multimerization. These lipid fingerprints are coupled to RAS dynamics, predicted to influence effector binding, and therefore may be a mechanism for regulating cell signaling cascades.
Iskandar Sitdikov, Jennifer Glick, et al.
APS March Meeting 2023
Jose Santos, Chen Wang, et al.
IEEE TNSM
Zhanhong Jiang, Kushal Mukherjee, et al.
ACC 2017
Christopher Giblin, Sean Rooney, et al.
BigData Congress 2021