Ribbon representation of the NMR structure for TAD-NCBD complex (pdb code: 2L14).

Abstract

<p>Helices α1, α2 and α3 of NCBD are colored with blue, cyan and green, respectively. Helices α4 and α5 of TAD are colored with yellow and red, respectively. N and C-terminal domains are labeled.large number of proteins (between 25% and 41%) are intrinsically disordered, however, these proteins also play important function in cell signaling and cancer upon binding with multiple interaction partners. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059627#pone.0059627-Liu1" target="_blank">[11]</a> In this study, NMR experiments indicate that apo-TAD is intrinsic disordered protein and apo-NCBD is not entirely unstructured with a helical molten globule <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059627#pone.0059627-Demarest1" target="_blank">[3] </a><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059627#pone.0059627-Wells1" target="_blank">[12]</a>. Upon binding each other, both NCBD and TAD undergo a transition from disordered to well folded. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059627#pone.0059627-Lee1" target="_blank">[10]</a> This suggests that both NCBD and TAD have significant conformational adjustment in complex. These experimental observations raise an interesting question if these intrinsic disordered NCBD and TAD obey an induced fit upon binding. To reveal this question, we utilize all atom molecular dynamics (MD) simulations in explicit solvent to analyze the coupling between binding and folding in the NCBD-TAD complex. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059627#pone.0059627-Henkels1" target="_blank">[13]</a>.</p