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Conformational dynamics of electrostatically charged Intrinsically Disordered Proteins

Schwarz, S.; Sarkar, S.; Sakhapov, D.; Sturm, A.; Wardetzky, M.; Enderlein, J.

2024-06-05 biophysics
10.1101/2024.06.04.597329 bioRxiv
Show abstract

We experimentally and computationally study the dynamics of homogeneously electrically charged intrinsically disordered proteins (IDPs) in ionic solutions (aqueous solutions containing salt). Computationally, this is achieved by extending a recently introduced discrete elastic rod (DER) model to include electrostatic interactions. The respective model includes only three free parameters: bending stiffness, bond length, and hydrodynamic radius. These parameters were obtained by fitting the measured conformational dynamics of uncharged polypeptides as reported in a previous publication [8]. We compare our computational results with photo-electron transfer fluorescence correlation spectroscopy (PET-FCS) measurements of the conformational dynamics of the highly charged (-44 e-) intrinsically disordered protein Prothymosin . We here report on an agreement between the loop-closing rates obtained from our computational model and the respective experimental measurements, with rate values significantly slower than those observed for uncharged IDPs.

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