Halogen Bonding-A Novel Interaction for Rational Drug Design?
Although recognized in small molecules for quite some time, the implications of halogen bonding in biomolecular systems are only now coming to light. In this study, several systems of proteins in complex with halogenated ligands have been investigated by using a two-layer QM/MM ONIOM methodology. In all cases, the halogen-oxygen distances are shown to be much less than the van der Waals radius sums. Singlepoint energy calculations unveil that the interaction becomes comparable in magnitude to classical hydrogen bonding. Furthermore, we found that the strength of the interactions attenuates in the order H≈ I>Br>Cl. These results agree well with the characteristics discovered within small model halogen-bonded systems. A detailed analysis of the interactions reveals that halogen bonding interactions are responsible for the different conformation of the molecules in the active site. This study would help to establish such interaction as a potential and effective tool in the context of drug design.
Yunxiang Lu Ting Shi Yong Wang Huaiyu Yang Xiuhua Yan Xiaoming Luo Hualiang Jiang Weiliang Zhu
Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences,
国际会议
武汉
英文
767-775
2010-09-01（万方平台首次上网日期，不代表论文的发表时间）