Lagüe P, Zuckermann M J, Roux B
Department of Chemistry, Université de Montréal, Montréal, Québec H3C 3J7, Canada.
Biophys J. 2000 Dec;79(6):2867-79. doi: 10.1016/S0006-3495(00)76524-6.
This study of lipid-mediated interactions between proteins is based on a theory recently developed by the authors for describing the structure of the hydrocarbon chains in the neighborhood of a protein inclusion embedded in a lipid membrane [Lagüe et al., Farad. Discuss. 111:165-172, 1998]. The theory involves the hypernetted chain integral equation formalism for liquids. The exact lateral density-density response function of the hydrocarbon core, extracted from molecular dynamics simulations of a pure dipalmitoylphosphatidylcholine bilayer based on an atomic model, is used as input. For the sake of simplicity, protein inclusions are modeled as hard repulsive cylinders. Numerical calculations were performed with three cylinder sizes: a small cylinder of 2.5-A radius, corresponding roughly to an aliphatic chain; a medium cylinder of 5-A radius, corresponding to a alpha-helical polyalanine protein; and a large cylinder of 9-A radius, representing a small protein, such as the gramicidin channel. The calculations show that the average hydrocarbon density is perturbed over a distance of 20-25 A from the edge of the cylinder for every cylinder size. The lipid-mediated protein-protein effective interaction is calculated and is shown to be nonmonotonic. In the case of the small and the medium cylinders, the lipid-mediated effective interaction of two identical cylinders is repulsive at an intermediate range but attractive at short range. At contact, there is a free energy of -2k(B)T for the 2.5-A-radius cylinder and -9k(B)T for the 5-A-radius cylinder, indicating that the association of two alpha-helices of both sizes is favored by the lipid matrix. In contrast, the effective interaction is repulsive at all distances in the case of the large cylinder. Results were obtained with two integral equations theories: hypernetted chain and Percus-Yevick. For the two theories, all results are qualitatively identical.
这项关于蛋白质间脂质介导相互作用的研究基于作者最近提出的一种理论，该理论用于描述嵌入脂质膜中的蛋白质包涵体附近烃链的结构[拉盖等人，《法拉第讨论》111:165 - 172，1998年]。该理论涉及液体的超网链积分方程形式。从基于原子模型的纯二棕榈酰磷脂酰胆碱双层分子动力学模拟中提取的烃核精确横向密度 - 密度响应函数用作输入。为了简单起见，蛋白质包涵体被建模为硬排斥圆柱体。使用三种圆柱体尺寸进行了数值计算：半径为2.5埃的小圆柱体，大致对应于一条脂肪链；半径为5埃的中圆柱体，对应于α - 螺旋聚丙氨酸蛋白质；以及半径为9埃的大圆柱体，代表一种小蛋白质，如短杆菌肽通道。计算表明，对于每种圆柱体尺寸，平均烃密度在距圆柱体边缘20 - 25埃的距离内受到扰动。计算了脂质介导的蛋白质 - 蛋白质有效相互作用，结果表明其是非单调的。对于小圆柱体和中圆柱体的情况，两个相同圆柱体的脂质介导有效相互作用在中间范围是排斥的，但在短距离是吸引的。在接触时，半径为2.5埃的圆柱体的自由能为 - 2k(B)T，半径为5埃的圆柱体的自由能为 - 9k(B)T，这表明脂质基质有利于这两种尺寸的两个α - 螺旋的缔合。相比之下，对于大圆柱体，有效相互作用在所有距离都是排斥的。使用两种积分方程理论获得了结果：超网链理论和珀库斯 - 耶维克理论。对于这两种理论，所有结果在定性上是相同的。
