Dubey Vikas, Prasanna Xavier, Sengupta Durba
Physical Chemistry Division, National Chemical Laboratory , Pune 411008, India.
J Phys Chem B. 2017 Mar 9;121(9):2111-2120. doi: 10.1021/acs.jpcb.6b09863. Epub 2017 Feb 22.
The insertion and association of membrane proteins is critical in several cellular processes. These processes were thought to be protein-driven, but increasing evidence points toward an important role of the lipid bilayer. The lipid-mediated contribution has been shown to be important in the association of membrane peptides, but the corresponding "lipophobic" component has not been directly estimated. Here, we calculate the free energy of insertion for transmembrane peptides and estimate the lipophobic component from the cost of cavity formation. The free-energy calculations were performed using the coarse-grain Martini force field, which has been successful in predicting membrane protein interactions. As expected, the charged moieties have the least favorable free energy of insertion and the highest cost of cavity formation. A length dependence was observed in polyalanine peptides with the lipid-mediated component increasing nonlinearly with peptide length. Membrane fluidity was tested by varying the temperature, and opposing effects were observed for short and long peptides. The dependence of the lipid-mediated effects on peptide length and temperature was not uniform and gives valuable insight into the anisotropic nature of the membrane. The results are an important step in estimating membrane effects in protein insertion and association.
膜蛋白的插入和缔合在多个细胞过程中至关重要。这些过程曾被认为是由蛋白质驱动的，但越来越多的证据表明脂双层起着重要作用。脂质介导的作用已被证明在膜肽的缔合中很重要，但相应的“疏脂”成分尚未得到直接评估。在此，我们计算跨膜肽的插入自由能，并从空穴形成成本估算疏脂成分。自由能计算使用了粗粒化的马蒂尼力场，该力场在预测膜蛋白相互作用方面很成功。正如预期的那样，带电部分的插入自由能最不利，空穴形成成本最高。在聚丙氨酸肽中观察到长度依赖性，脂质介导的成分随肽长度呈非线性增加。通过改变温度测试膜流动性，观察到短肽和长肽有相反的效应。脂质介导效应对肽长度和温度的依赖性并不一致，这为膜的各向异性性质提供了有价值的见解。这些结果是估算蛋白质插入和缔合中膜效应的重要一步。
