Intrinsically disordered proteins (IDPs) are a kind of special proteins discovered in recent years. They have no definite three-dimensional structure under natural conditions, but have normal biological functions. They are widely involved in signal transduction, DNA transcription, cell division and other important processes. The discovery of IDPs not only challenges and complements the traditional protein "sequence-structure-function" paradigm, but also provides new ideas for the treatment of many diseases. Recently, Prof. Liu Zhirong's group and Prof. Lai Luhua have collaborated to reveal a new "cloud" interaction mode between IDPs and small-molecule ligands.

    IDPs are potential drug targets. Due to the lack of single structure of IDPs, it is difficult to accurately characterize their characteristics in experiments. In order to study the interaction mode between IDPs and ligand small molecule, the team used computer molecular simulation method to study the interaction between the oncoprotein c-myc and its inhibitor ligand. The results showed that the c-myc remained disordered even after binding to the ligand. Different from the stable pocket structure formed by traditional protein-ligand binding, small ligand molecules bind to multiple discrete sites of c-myc with a certain probability. In order to characterize this new binding property, the team proposed the concept of "ligand cloud", suggesting that the interaction between natural disordered proteins and ligands is carried out in the way of "ligand cloud around protein cloud" (see figure below). The concept of ligand cloud highlights the special selectivity and specificity of IDPs in the binding process.

    The work was published as a cover article in PLoS computational biology:

Fan Jin, Chen Yu, luhuai Lai *, and Zhirong Liu* (2013) Ligand clouds around protein clouds: a scenario of ligand binding with intrinsically disordered proteins. PLoS Computational Biology 9 (10): e1003249/1-11.

The first author of this paper is Fan Jin (2013 graduate, supervised by Prof. Liu), and the second author is Yu Chen (supervised by Prof. Lai).

Link: Fan Jin, Chen Yu, Luhua Lai*, and Zhirong Liu*. Ligand clouds around protein clouds: a scenario of ligand binding with intrinsically disordered proteins. PLoS Comput. Biol. 9 (10), e1003249/1-11 (2013).

Media reports:
PKU news: http://pkunews.pku.edu.cn/xwzh/2013-11/08/content_279605.htm
CCME@PKU: http://www.chem.pku.edu.cn/news.php?id=3882
CQB@PKU: http://cqb.pku.edu.cn/hd/252898.shtml
Science and technology development center of the Ministry of Education:: http://www.cutech.edu.cn/cn/gxkj/2013/11/1382603037887656.htm