Macrocyclization is a critical strategy in rational drug design that can offer several advantages, such as enhancing binding affinity, increasing selectivity, and improving cellular permeability. Herein, we introduce MacGen, a web tool devised for structure-based macrocycle design. MacGen identifies exit vector pairs within a ligand that are suitable for cyclization and finds 3D linkers that can align with the geometric arrangement of these pairs to form macrocycles. To aid in the fast acquisition of appropriate linkers, we have built an indexed 3D linker database that includes linkers of various lengths and categories. MacGen provides comprehensive configurable parameters that enable users to obtain preferred linkers, meeting unique requirements in practical ligand design scenarios. We hope MacGen will serve as a handy tool that can rapidly explore potential macrocycle space. The MacGen server is freely accessible at https://macgen.xundrug.cn.

中文翻译：

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MacGen：用于基于结构的大周期设计的 Web 服务器。


大环化是合理药物设计中的一种关键策略，具有多种优势，例如增强结合亲和力、增加选择性和提高细胞通透性。在本文中，我们介绍了 MacGen，这是一个专为基于结构的大周期设计而设计的 Web 工具。MacGen 识别配体中适合环化的出口载体对，并找到可以与这些对的几何排列对齐以形成大环的 3D 接头。为了帮助快速获取合适的链接器，我们构建了一个索引 3D 链接器数据库，其中包括各种长度和类别的链接器。MacGen 提供全面的可配置参数，使用户能够获得首选的接头，满足实际配体设计场景中的独特要求。我们希望 MacGen 能成为一个方便的工具，可以快速探索潜在的大循环空间。MacGen 服务器可在 https://macgen.xundrug.cn 免费访问。