MacGen: A Web Server\nfor Structure-Based Macrocycle\nDesign

Macrocyclization is a critical strategy in rational drug\ndesign\nthat can offer several advantages, such as enhancing binding affinity,\nincreasing selectivity, and improving cellular permeability. Herein,\nwe introduce MacGen, a web tool devised for structure-based macrocycle\ndesign. MacGen identifies exit vector pairs within a ligand that are\nsuitable for cyclization and finds 3D linkers that can align with\nthe geometric arrangement of these pairs to form macrocycles. To aid\nin the fast acquisition of appropriate linkers, we have built an indexed\n3D linker database that includes linkers of various lengths and categories.\nMacGen provides comprehensive configurable parameters that enable\nusers to obtain preferred linkers, meeting unique requirements in\npractical ligand design scenarios. We hope MacGen will serve as a\nhandy tool that can rapidly explore potential macrocycle space. The\nMacGen server is freely accessible at https://macgen.xundrug.cn.