Multiscale simulation of the interaction of calreticulin-thrombospondin-1 complex with a model membrane microdomain

Cell surface calreticulin( CRT) binding to thrombospondin-1(TSP1), regulates cell adhesion, migration, anoikisresistance, and collagen production. Due to the essential role of membrane microdomains in CRT-mediated focal adhesiondisassembly, we previously studied the effect of raft-like bilayers on TSP1– CRTinteractions with all-atom molecular dynamics (AAMD) simulations. However, the simulated systems of protein on the surface of the bilayer(s) in the explicit solvent are too large for long timescale AAMD simulations due to computational expense. In this study, we adopted a multiscale modelingapproach of combining AAMD, coarse-grained molecule dynamics (CGMD), and reversed AAMD (REV AAMD) simulations to investigate the interactions of single CRTor of the TSP1– CRTcomplex with a membrane microdomain at microsecondtimescale. Results showed that CRTconformational stabilization by binding of TSP1 in AAMD simulation was undetectable in CGMD simulation, but it was recovered in REV AAMD simulation. Simila...