Transient pockets on protein surfaces involved in protein-protein interaction
Transient pockets on protein surfaces involved in protein-protein interaction
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DOI：
10.1021/jm070095g
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发表时间：
2007-07-26
影响因子：
7.3
通讯作者：
Helms, Volkhard
中科院分区：
文献类型：
--
作者：
Eyrisch, Susanne;Helms, Volkhard
新的口袋检测方案成功识别了 BCL-X-L、IL-2 和 MDM2 蛋白质表面上的瞬时口袋。由于未结合的蛋白质中不存在天然抑制剂结合袋或仅部分可检测到，因此这些晶体结构被用作 10 ns 长分子动力学模拟的起点。使用程序 PASS 扫描轨迹快照以查找蛋白质表面上的空腔。检测到的空腔被聚集起来以确定几个不同的瞬态空穴。它们都在 2.5 ps 内打开，并且大多数出现了多次。总体而言，所有三个系统都给出了相似的结果。在天然结合位点，所有三个系统都可以观察到与已知抑制剂结合的类似大小的口袋。 AutoDock 可以成功地将抑制剂分子放入这些瞬态口袋中，与其晶体结构的偏差小于 2 A rms，表明该协议作为识别蛋白质表面上的瞬态配体结合口袋的可行工具。
A new pocket detection protocol successfully identified transient pockets on the protein surfaces of BCL-X-L, IL-2, and MDM2. Because the native inhibitor binding pocket was absent or only partly detectable in the unbound proteins, these crystal structures were used as starting points for 10 ns long molecular dynamics simulations. Trajectory snapshots were scanned for cavities on the protein surface using the program PASS. The detected cavities were clustered to determine several distinct transient pockets. They all opened within 2.5 ps, and most of them appeared multiple times. All three systems gave similar results overall. At the native binding site, pockets of similar size compared with a known inhibitor bound could be observed for all three systems. AutoDock could successfully place inhibitor molecules into these transient pockets with less than 2 A rms deviation from their crystal structures, suggesting this protocol as a viable tool to identify transient ligand binding pockets on protein surfaces.