MolHyb: A Web Server for Structure-Based Drug Design by Molecular Hybridization

• Published in: Journal of chemical information and modeling 2022-06, Vol.62 (12), p.2916-2922
• Main Authors: Wang, Hao, Pan, Xiaolin, Zhang, Yueqing, Wang, Xingyu, Xiao, Xudong, Ji, Changge
• Format: Article
• Language: English
• Subjects: Chemical bonds; Chemical compounds; Crystal structure; Hybridization; Ligands; Molecular structure; Proteins; Servers
• ISSN: 1549-9596; 1549-960X
• DOI: 10.1021/acs.jcim.2c00443

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/.