Marques Sérgio M, Borko Simeon, Vavra Ondrej, Dvorsky Jan, Kohout Petr, Kabourek Petr, Hejtmanek Lukas, Damborsky Jiri, Bednar David
Loschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, 62500 Brno, Czech Republic.
International Clinical Research Center, St. Anne's University Hospital Brno, 65691 Brno, Czech Republic.
Nucleic Acids Res. 2025 Jul 7;53(W1):W132-W142. doi: 10.1093/nar/gkaf399.
Enzymes with buried active sites utilize molecular tunnels to exchange substrates, products, and solvent molecules with the surface. These transport mechanisms are crucial for protein function and influence various properties. As proteins are inherently dynamic, their tunnels also vary structurally. Understanding these dynamics is essential for elucidating structure-function relationships, drug discovery, and bioengineering. Caver Web 2.0 is a user-friendly web server that retains all Caver Web 1.0 functionalities while introducing key improvements: (i) generation of dynamic ensembles via automated molecular dynamics with YASARA, (ii) analysis of dynamic tunnels with CAVER 3.0, (iii) prediction of ligand trajectories in multiple snapshots with CaverDock 1.2, and (iv) customizable ligand libraries for virtual screening. Users can assess protein flexibility, identify and characterize tunnels, and predict ligand trajectories and energy profiles in both static and dynamic structures. Additionally, the platform supports virtual screening with FDA/EMA-approved drugs and user-defined datasets. Caver Web 2.0 is a versatile tool for biological research, protein engineering, and drug discovery, aiding the identification of strong inhibitors or new substrates to bind to the active sites or tunnels, and supporting drug repurposing efforts. The server is freely accessible at https://loschmidt.chemi.muni.cz/caverweb.
具有埋藏活性位点的酶利用分子隧道与表面交换底物、产物和溶剂分子。这些运输机制对蛋白质功能至关重要，并影响各种特性。由于蛋白质本质上是动态的，它们的隧道在结构上也各不相同。了解这些动态对于阐明结构 - 功能关系、药物发现和生物工程至关重要。Caver Web 2.0是一个用户友好的网络服务器，它保留了Caver Web 1.0的所有功能，同时引入了关键改进：（i）通过使用YASARA的自动分子动力学生成动态集合，（ii）使用CAVER 3.0分析动态隧道，（iii）使用CaverDock 1.2在多个快照中预测配体轨迹，以及（iv）用于虚拟筛选的可定制配体库。用户可以评估蛋白质的灵活性，识别和表征隧道，并预测静态和动态结构中的配体轨迹和能量分布。此外，该平台支持使用FDA/EMA批准的药物和用户定义的数据集进行虚拟筛选。Caver Web 2.0是用于生物学研究、蛋白质工程和药物发现的多功能工具，有助于识别与活性位点或隧道结合的强效抑制剂或新底物，并支持药物重新利用的努力。该服务器可在https://loschmidt.chemi.muni.cz/caverweb免费访问。
