The impact of bilayer composition on the dimerization properties of the Slg1 stress sensor TMD from a multiscale...

The impact of mutual interactions between the transmembrane domains of membrane proteins and lipids on bilayer properties has gained major attraction. Most simulation studies of membranes rely on the Martini force field, which has proven extremely helpful in providing molecular insights into realistic systems. Accordingly, an evaluation of the accuracy of the Martini force field is crucial to be able to correctly interpret the reported data. In this study, we combine atomistic and coarse-grained Martini simulations to investigate the properties of transmembrane domains (TMDs) in a model yeast membrane. The results show that the TMD binding state (monomeric and dimeric with positive or negative crossing angle) and the membrane composition significantly influence the properties around the TMDs and change TMD-TMD and TMD-lipid affinities. Furthermore, ergosterol (ERG) exhibits a strong affinity to TMD dimers. Importantly, the right-handed TMD dimer configuration is stabilized via TMD-TMD contacts by the addition of asymmetric anionic phosphatidylserine (PS). The coarse-grained simulations corroborate many of these findings, with two notable exceptions: a systematic overestimation of TMD-ERG interaction and lack of stabilization of the right-handed TMD dimers with the addition of PS.