Intrinsically disordered protein (IDP) dynamics are strongly influenced by specific residue-residue interactions and solvent effects. Placing two minimally invasive probes (a tryptophan and a cysteine) at various positions within an IDP sequence, and using photo-induced electron transfer (PET) to measure the rate of contact between them, is a powerful way to reveal interactions affecting specific regions of the IDP. Combining PET and all-atom MD simulations, we recently identified key transient interactions that dictate the dynamics of measles virus N TAIL , and can explain functional aspects of viral transcription and replication (https://doi.org/10.1101/2024.07.22.604679). In previous work presented at this meeting, we investigated how PET measurements are affected by the presence of dangling ends, when the probes are placed inside the sequence rather than at the very ends of a polypeptide chain. A simple homopolymer theory (with excluded volume interactions) of polymer dynamics captured the general trends observed in experimental PET data of model peptides, with the relaxation rates slowing down as a function of dangling end length. Here, we focus on understanding the pronounced saturation effect observed in the PET data as the dangling end size approaches the sequence separation between the probes |i-j| and how this is affected by chain interactions. Using our model, we now explore how charge and non-charge sequence properties couple with the physics of dangling ends and impact relaxation times. To further investigate the effect of sequence-dependent interactions in our model peptides, we compare experimental PET data to those calculated from extensive all-atom MD simulations, using different force-fields validated by additional CD data. We discuss how specific interactions influence backbone relaxation times and contact formation times, for segments at the center of the chain, compared to those towards the ends.
Ottoway et al. (2026) studied this question.