Department of Physics and Astronomy, University of Delaware, Newark, Delaware.
Department of Physics and Astronomy, University of Delaware, Newark, Delaware; Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware.
Biophys J. 2021 May 4;120(9):1777-1787. doi: 10.1016/j.bpj.2021.02.029. Epub 2021 Feb 26.
Preferential lipid solvation of the G-protein-coupled A adenosine receptor (AR) is evaluated from 35 μs of all-atom molecular dynamics simulation. A coarse-grained transition matrix algorithm is developed to overcome slow equilibration of the first solvation shell, obtaining estimates of the free energy of solvation by different lipids for the receptor in different activation states. Results indicate preference for solvation by unsaturated chains, which favors the active receptor. A model for lipid-dependent G-protein-coupled receptor activity is proposed in which the chemical potential of lipids in the bulk membrane modulates receptor activity. The entropies associated with moving saturated and unsaturated lipids from bulk to AR's first solvation shell are evaluated. Overall, the acyl chains are more disordered (i.e., obtain a favorable entropic contribution) when partitioning to the receptor surface, and this effect is augmented for the saturated chains, which are relatively more ordered in bulk.
通过 35 μs 的全原子分子动力学模拟评估 G 蛋白偶联 A 腺苷受体 (AR) 的优先脂质溶解。开发了一种粗粒转换矩阵算法来克服第一溶剂化壳的缓慢平衡，从而获得不同激活状态下受体对不同脂质的溶剂化自由能的估计。结果表明，对不饱和链的溶解具有偏好性，这有利于活性受体。提出了一种基于脂质的 G 蛋白偶联受体活性模型，其中在大块膜中的脂质的化学势调节受体活性。评估了将饱和和不饱和脂质从大块转移到 AR 的第一溶剂化壳时的熵。总体而言，当分配到受体表面时，酰基链更加无序（即，获得有利的熵贡献），并且对于在大块中相对更有序的饱和链，这种效应得到增强。
