Fig 6. Simulation results of intermediate conformation states between the closed and open Gαs structures obtained using elastic network interpolation (ENI).

(A) Possible states of Gαs. A large conformational change was observed around the GαsAH domain showing the swing motion with respect to the fixed GαsRas domain. (B) Root-mean-square deviation and cost function values of all intermediate conformational states with respect to the initial, closed Gαs structure. The smooth changes in both values represent the conformational changes and fluctuations in energy between the two reference structures of Gαs well. (C) Mobility changes during the transition. Intermediate conformations were more flexible than the two endpoint structures. Particularly, the mobility of the nucleotide-binding pocket region kept increasing during the transition. (D) Verification of the ENI pathway of the Gαs structure using the cumulative overlap values between the set of first 5% lowest normal modes and the directional vector to the target structure from each intermediate.