Disordered Motifs and Domains in Cell Control - October 11-15, 2014

Disordered Motifs and Domains in Cell Control

Sunday Speaker Abstracts

Interaction Specificity of Intrinsically Disordered Proteins Zhirong Liu . Peking University, Beijing, China.

Interaction specificity of proteins is critical to their cellular function. Due to their chain flexibility, whether intrinsically disordered proteins (IDPs) possess high specificity is in debate. We conducted some investigations on this question. Firstly, by combining an analysis on mutant data in the literature and a simulation with a coarse-grained model, we found that that the enthalpy–entropy compensation for disordered protein complexes was more complete than that for ordered protein complexes. Interactions of IDPs are more malleable than those of ordered proteins due to their structural flexibility in the complex. Secondly, we performed extensive all- atom simulations on the segment 370-409 of the oncoprotein c-Myc and its binding to an inhibitor. Upon binding of the ligand, c-Myc remained disordered. The ligand was found to bind to c-Myc at different sites along the chain and may be described as “ligand clouds around protein clouds”, which is different from the more rigid cases that usually result in a dominant bound structure. Finally, the drug design concerning IDPs is briefly discussed.

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