Shanghai Engineering Research Center for Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China.
J Chem Inf Model. 2022 Jun 27;62(12):2916-2922. doi: 10.1021/acs.jcim.2c00443. Epub 2022 Jun 13.
Molecular hybridization is a widely used ligand design method in drug discovery. In this study, we present MolHyb, a web server for structure-based ligand design by molecular hybridization. The input of MolHyb is a protein file and a seed compound file. MolHyb tries to generate novel ligands through hybridizing the seed compound with helper compounds that bind to the same protein target or similar proteins. To facilitate the job of getting helper compounds, we compiled a modeled protein-ligand structure database as an extension to crystal structures in the PDB database by placing the bioactive compounds in ChEMBL into their corresponding 3D protein binding pocket properly. MolHyb works by searching for helper compounds from the protein-ligand structure database and migrating chemical moieties from helper compounds to the seed compound efficiently. Hybridization is performed at both cyclic and acyclic bonds. The users can also input their own helper compounds to MolHyb. We hope that MolHyb will be a useful tool for rational drug design. MolHyb is freely available at http://molhyb.xundrug.cn/.
分子杂交是药物发现中广泛使用的配体设计方法。在这项研究中，我们提出了 MolHyb，这是一个基于结构的配体设计的网络服务器，通过分子杂交。MolHyb 的输入是一个蛋白质文件和一个种子化合物文件。MolHyb 试图通过将种子化合物与结合到同一蛋白质靶标或类似蛋白质的辅助化合物杂交来生成新的配体。为了方便获取辅助化合物的工作，我们通过将 ChEMBL 中的生物活性化合物适当地放入其相应的 3D 蛋白质结合口袋中，将一个模拟的蛋白质-配体结构数据库作为 PDB 数据库中晶体结构的扩展进行编译。MolHyb 通过从蛋白质-配体结构数据库中搜索辅助化合物，并有效地将化学部分从辅助化合物迁移到种子化合物来工作。杂交在环状和非环状键上都可以进行。用户也可以向 MolHyb 输入自己的辅助化合物。我们希望 MolHyb 将成为合理药物设计的有用工具。MolHyb 可在 http://molhyb.xundrug.cn/ 免费获得。
