Transmembrane Protein Docking with JabberDock

Transmembrane proteins act as an
intermediary for a broad range
of biological process. Making up 20% to 30% of the proteome, their
ubiquitous nature has resulted in them comprising 50% of all targets
in drug design. Despite their importance, they make up only 4% of
all structures in the PDB database, primarily owing to difficulties
associated with isolating and characterizing them. Membrane protein
docking algorithms could help to fill this knowledge gap, yet only
few exist. Moreover, these existing methods achieve success rates
lower than the current best soluble proteins docking software. We
present and test a pipeline using our software, JabberDock, to dock
membrane proteins. JabberDock docks shapes representative of membrane
protein structure and dynamics in their biphasic environment. We verify
JabberDock’s ability to yield accurate predictions by applying
it to a benchmark of 20 transmembrane dimers, returning a success
rate of 75.0%. This makes our software very competitive among available
membrane protein–protein docking tools.

跨膜蛋白（Transmembrane proteins）是诸多生物学过程的媒介。这类蛋白占蛋白质组（proteome）的20%~30%，分布遍及各类生物系统，因此在药物设计的全部靶点中占比高达50%。尽管跨膜蛋白具有重要价值，但其在PDB数据库（Protein Data Bank）的所有收录结构中仅占4%，这主要源于分离和表征这类蛋白存在诸多技术难题。
膜蛋白对接算法有望填补这一研究空白，但目前相关方法十分有限。此外，现有膜蛋白对接工具的预测成功率均低于当前最优的可溶性蛋白（soluble proteins）对接软件。
本研究提出并测试了一套基于自研软件JabberDock的膜蛋白对接流程。JabberDock可在膜蛋白所处的双相环境中，对表征其结构与动态特征的模型进行对接模拟。我们将该工具应用于包含20个跨膜二聚体的基准测试集以验证其精准预测能力，最终获得了75.0%的预测成功率。这使得JabberDock在现有膜蛋白-蛋白对接工具中具备显著的竞争力。