Studies on sensitivity to tension and gating pathway of MscL by molecular dynamic simulation

Abstract

Mechanosensitive (MS) ion channels play an important role in various physiological processes. Although the determination of the structure of mechanosensitive channel of large conductance (MscL) makes the simulation study possible, it has not so far been possible to directly simulate the gating mechanism of MscL in atomic detail. In this article, MscL has been studied via molecular dynamic (MD) simulations to gain a detailed description of the sensitivity to lateral tension and the gating pathway. MscL undergoes conformational rearrangement in sustaining lateral tension, and the open state is obtained when 2.0MPa lateral tension is directly applied on the pure protein. During the opening process, Loop region responds to tension first, and the mechanical sensitivity is followed by S1 domain. Transmembrane (TM) bundle is the key position for channel opening, and the motion of TM1 helices finally realizes the significant expansion of the constricted gating pore. C-terminus domain presents expansion later during the TM opening. In our study, return of the whole protein to the initial closed state is achieved only in the early opening stage. During the relaxation from the open state, the TM helices are the most mobile domain, which is different from the opening process.