Assembly of Protein Complexes in and on the Membrane with Predicted Spatial Arrangement Constraints
Assembly of Protein Complexes in and on the Membrane with Predicted Spatial Arrangement Constraints
复制标题
DOI：
10.1016/j.jmb.2024.168486
复制
发表时间：
2024-02-16
影响因子：
5.6
通讯作者：
Kihara，Daisuke
中科院分区：
文献类型：
--
作者：
Christoffer，Charles;Harini，Kannan;Kihara，Daisuke
膜蛋白在各种细胞过程中发挥着至关重要的作用，它们与膜内和膜上其他蛋白质的相互作用对于它们的正常功能至关重要。虽然越来越多的膜蛋白结构正在被确定，但可用的结构数据仍然很少。为了深入了解膜蛋白复合物的机制，由于实验测定的挑战，计算对接方法是必要的。在这里，我们介绍 Mem-LZerD，一种刚体膜对接算法，旨在利用现代膜建模和蛋白质对接技术来促进膜蛋白复合物的对接。 Mem-LZerD基于LZerD蛋白质对接算法，在多轮CAPRI蛋白质对接评估中始终名列前茅。通过采用几何散列、新受预测膜高度和倾斜角度约束以及考虑膜插入能量的模型评分的组合，我们证明了 Mem-LZerD 模拟不同膜蛋白-蛋白复合物的能力。 Mem-LZerD 在既定基准中成功对 21 个跨膜复合物中的 13 个（61.9%）进行了非结合对接，比以前的方法显示的要多。它还在 44 个跨膜复合物和 92 个外周膜蛋白复合物的新数据集上进行了测试，分别成功模拟了 35 个（79.5%）和 15 个（16.3%）复合物。当包括外围目标的非盲定向时，成功次数增加到 54 次（58.7%）。我们进一步证明 Mem-LZerD 可以生成适合分子动力学模拟的复杂模型。 Mem-LZerD 可在 https://lzerd.kiharalab.org 上获取。
Membrane proteins play crucial roles in various cellular processes, and their interactions with other proteins in and on the membrane are essential for their proper functioning. While an increasing number of structures of more membrane proteins are being determined, the available structure data is still sparse. To gain insights into the mechanisms of membrane protein complexes, computational docking methods are necessary due to the challenge of experimental determination. Here, we introduce Mem-LZerD, a rigid-body membrane docking algorithm designed to take advantage of modern membrane modeling and protein docking techniques to facilitate the docking of membrane protein complexes. Mem-LZerD is based on the LZerD protein docking algorithm, which has been constantly among the top servers in many rounds of CAPRI protein docking assessment. By employing a combination of geometric hashing, newly constrained by the predicted membrane height and tilt angle, and model scoring accounting for the energy of membrane insertion, we demonstrate the capability of Mem-LZerD to model diverse membrane protein–protein complexes. Mem-LZerD successfully performed unbound docking on 13 of 21 (61.9%) transmembrane complexes in an established benchmark, more than shown by previous approaches. It was additionally tested on new datasets of 44 transmembrane complexes and 92 peripheral membrane protein complexes, of which it successfully modeled 35 (79.5%) and 15 (16.3%) complexes respectively. When non-blind orientations of peripheral targets were included, the number of successes increased to 54 (58.7%). We further demonstrate that Mem-LZerD produces complex models which are suitable for molecular dynamics simulation. Mem-LZerD is made available at https://lzerd.kiharalab.org.