The mechanosensitive channels of large conductance (MscL) are bacterial membrane proteins that serve as last resort emergency release valves in case of severe osmotic downshock. Sensing bilayer tension, MscL channels are sensitive to changes in the bilayer environment and are, therefore, an ideal test case for exploring membrane protein coupling. Here, we use high-throughput coarse-grained molecular dynamics simulations to characterize MscL gating kinetics in different bilayer environments under the influence of alcohols. We performed over five hundred simulations to obtain sufficient statistics to reveal the subtle effects of changes in the membrane environment on MscL gating. MscL opening times were found to increase with the addition of the straight chain alcohols ethanol, octanol, and to some extent dodecanol but not with hexadecanol. Increasing concentration of octanol increased the impeding effect, but only up to 10-20 mol %. Our in silico predictions were experimentally confirmed using reconstituted MscL in a liposomal fluorescent efflux assay. Our combined data reveal that the effect of alcohols on MscL gating arises not through specific binding sites but through a combination of the alcohol-induced changes to a number of bilayer properties and their alteration of the MscL bilayer interface. Our work provides a key example of how extensive molecular simulations can be used to predict the functional modification of membrane proteins by subtle changes in their bilayer environment.