Extension of a protein docking algorithm to membranes and applications to amyloid precursor protein dimerization.
Extension of a protein docking algorithm to membranes and applications to amyloid precursor protein dimerization.
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作者：
Viswanath S;Dominguez L;Foster LS;Straub JE;Elber R
新的调整引入对接算法，DOCK/PIERR，用于预测跨膜蛋白复合物的结构。显示出关于膜环境的知识显著提高对接精度。扩展版本的DOCK/PIERR被证明可以执行与其他主要对接软件包的兼容。这种膜版本的DOCK/PIERR适用于预测的卷曲螺旋同源二聚体结构的跨膜区的C-末端肽的淀粉样前体蛋白（C99）。从分子动力学模拟的结果C99同源二聚体在POPC双层和对接进行了比较。对接的结果被发现捕获的同二聚体合奏的关键方面，包括存在三个拓扑结构不同的构象。此外，扩展版本的DOCK/PIERR是成功地捕捉在膜和胶束溶剂化的影响。具体而言，DOCK/PIERR再现的同二聚体合奏模拟POPC双层和DPC胶束，其中构型熵和表面曲率效应的偏向手性和拓扑结构的同二聚体合奏的本质区别。
Novel adjustments are introduced to the docking algorithm, DOCK/PIERR, for the purpose of predicting structures of transmembrane protein complexes. Incorporating knowledge about the membrane environment is shown to significantly improve docking accuracy. The extended version of DOCK/PIERR is shown to perform comparably to other leading docking packages. This membrane version of DOCK/PIERR is applied to the prediction of coiled-coil homodimer structures of the transmembrane region of the C-terminal peptide of amyloid precursor protein (C99). Results from MD simulation of the C99 homodimer in POPC bilayer and docking are compared. Docking results are found to capture key aspects of the homodimer ensemble, including the existence of three topologically distinct conformers. Furthermore, the extended version of DOCK/PIERR is successful in capturing the effects of solvation in membrane and micelle. Specifically, DOCK/PIERR reproduces essential differences in the homodimer ensembles simulated in POPC bilayer and DPC micelle, where configurational entropy and surface curvature effects bias the handedness and topology of the homodimer ensemble.