Flat or angular? The impact of the nitrogen atom hybridization on the docking results for arylpiperazine derivatives as an example

作     者：Rzesikowska, Katarzyna Jablonski, Mateusz Kalinowska-Tluscik, Justyna 

作者机构：Jagiellonian Univ Dept Crystal Chem & Crystal Phys Fac Chem Gronostajowa 2 PL-30387 Krakow Poland 

出 版 物：《STRUCTURAL CHEMISTRY》 (结构化学)

年 卷 期：2020年第31卷第2期

页      面：823-829页

核心收录：

学科分类：07[理学] 0703[理学-化学] 

基　　金：ACC Cyfronet AGH 

主　　题：Arylpiperazine derivatives 3D structure prediction Virtual screening 

摘      要：Structure-based virtual screening has become a standard approach in modern drug discovery. It involves molecular docking and estimation of the ligand binding likelihood based on the scoring function. Surprisingly, in the search for new pharmaceuticals, one of the bottlenecks can be the ligand s 3D structure prediction, especially for molecules with amine groups. In our work, the impact of the nitrogen atom hybridization in arylpiperazine derivatives on the results of docking to serotonin receptor type 7 is discussed. Our docking/re-docking studies show that the nitrogen lone pair may be involved in weak ligand-protein interactions. The presented results suggest that assumption of amine group planarity in the arylpiperazine 3D structure prediction may be a misleading factor in computer-aided drug discovery, influencing active conformation prediction. With our paper, we would like to raise awareness that in the case of compounds with amine groups, special care must be taken in the 3D ligand s structure preparation for molecular docking studies.