Gating　transition　of　the　mechanosensitive　channel　of　large　conductance　(MscL)　represents　a　good　example　of　important　biological　processes　that　are　difficult　to　describe　using　atomistic　simulations　due　to　the　large　(submicron)　length　scale　and　long　(millisecond)　time　scale.　Here　we　develop　a　novel　computational　framework　that　tightly　couples　continuum　mechanics　with　continuum　solvation　models　to　study　the　detailed　gating　behavior　of　E.　coli-MscL.　The　components　of　protein　molecules　are　modeled　by　continuum　elements　that　properly　describe　their　shape,　material　properties　and　physicochemical　features　(e.g.,　charge　distribution).　The　lipid　membrane　is　modeled　as　a　three-layer　material　in　which　the　lipid　head　group　and　tail　regions　are　treated　separately,　taking　into　account　the　fact　that　fluidic　lipid　bilayers　do　not　bear　shear　stress.　Coupling　between　mechanical　and　chemical　responses　of　the　channel　is　realized　by　an　iterative　integration　of　continuum　mechanics　(CM)　modeling　and　continuum　solvation　(CS)　computation.　Compared　to　previous　continuum　mechanics　studies,　the　present　model　is　capable　of　capturing　the　most　essential　features　of　the　gating　process　in　a　much　more　realistic　fashion:　due　mainly　to　the　apolar　solvation　contribution,　the　membrane　tension　for　full　opening　of　MscL　is　reduced　substantially　to　the　experimental　measured　range.　Moreover,　the　pore　size　stabilizes　constantly　during　gating　because　of　the　intricate　interactions　of　the　multiple　components　of　the　system,　implying　the　mechanism　for　sub-conducting　states　of　MscL　gating.　A　significant　fraction　(similar　to　2/3)　of　the　gating　membrane　strain　is　required　to　reach　the　first　sub-conducting　state　of　our　model,　which　is　featured　with　a　relative　conductance　of　0.115　to　the　fully　opened　state.　These　trends　agree　well　with　experimental　observations.　We　anticipate　that　the　coupled　CM/CS　modeling　framework　is　uniquely　suited　for　the　analysis　of　many　biomolecules　and　their　assemblies　under　external　mechanical　stimuli.