Publications by authors named "Jordan A P McIvor"

Structural disorder in proteins is central to cellular signaling, where conformational plasticity equips molecules to promiscuously interact with different partners. By engaging with multiple binding partners via the rearrangement of its three helices, the nuclear coactivator binding domain (NCBD) of the CBP/p300 transcription factor is a paradigmatic example of promiscuity. Recently, molecular simulations and experiments revealed that, through the establishment of long-range electrostatic interactions, intended as salt-bridges formed between the post-translationally inserted phosphate and positively charged residues in helix H3 of NCBD, phosphorylation triggers NCBD compaction, lowering its affinity for binding partners.

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More than 1600 human transcription factors orchestrate the transcriptional machinery to control gene expression and cell fate. Their function is conveyed through intrinsically disordered regions (IDRs) containing activation or repression domains but lacking quantitative structural ensemble models prevents their mechanistic decoding. Here we integrate single-molecule FRET and NMR spectroscopy with molecular simulations showing that DNA binding can lead to complex changes in the IDR ensemble and accessibility.

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We simulated the dynamics of a set of peptides characterized by ensembles rich in PPII-helical content, to assess the ability of the most recent Kirkwood-Buff force field (KBFF20) to sample this conformational peculiarity. KBFF has been previously shown to capably reproduce experimental dimensions of disordered proteins, while being limited in confidently sampling structured proteins. Further development of the force field bridged this gap.

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