An approach for the efficient simulation of phase-separated lipid bilayers, for use in the calculation of equilibrium free energies of partitioning between lipid domains, is proposed. The methodology exploits restraint potentials and rectangular aspect ratios that enforce lipid phase separation, allowing for the simulation of smaller systems that approximately reproduce bulk behavior. The utility of this approach is demonstrated through the calculation of potentials of mean force for the translation of a transmembrane protein between lipid domains. The impact of the imposed restraints on lipid tail ordering and lipid packing are explored, providing insight into how restraints can best be employed to compute accurate free-energy surfaces. This approach should be useful in the accurate calculation of equilibrium partition coefficients for transmembrane protein partitioning in heterogeneous membranes, providing insight into the thermodynamic driving forces that control this fundamental biophysical phenomenon.

提出了一种有效模拟相分离脂质双层的方法，用于计算脂质域之间分配的平衡自由能。该方法利用约束电位和矩形纵横比来强制脂质相分离，从而允许模拟近似再现整体行为的较小系统。通过计算跨膜蛋白在脂质结构域之间平移的平均力的潜力，证明了这种方法的实用性。探讨了施加的限制对脂质尾部排序和脂质堆积的影响，深入了解如何最好地利用限制来计算准确的自由能表面。这种方法应该有助于准确计算异质膜中跨膜蛋白分配的平衡分配系数，从而深入了解控制这一基本生物物理现象的热力学驱动力。