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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