Extracting Sequence-Dependent Intra-Protein Interaction Parameters from Photo-Induced Electron Transfer Measurements of IDPs

Abstract

A fundamental understanding of structure/dynamics and function of intrinsically disordered proteins (IDPs), analogous to that reached for protein folding, requires experimental data that can be directly linked to physics based models. Photo-induced electron transfer (PET) measurements between tryptophan and cysteine offer a convenient method to measure end-to-end contact formation probabilities and rates in IDPs. This data can be directly linked to models describing IDP structure and dynamics in terms of intra-protein interactions. The information provided is similar to that of FRET and FCS, without the need to label the IDP with prosthetic dyes. To understand sequence-specific intra-protein interactions, we have generated a wide set of PET data for different IDP variants under a range of solvent conditions. However, the inferred average properties strongly depend on the distribution function chosen to describe the end-to-end distance. Moreover, IDPs with different sequences or under different physico-chemical conditions might require different distribution functions. We therefore analyze the data set by applying a polymer model that allows variations of the distribution function. We are able to explain all the data by separating position-dependent electrostatic contributions from non-electrostatic contributions, including solvent effects. The results shed light on the amino acid based interaction parameters that can be used for both future experimental and theoretical studies of IDPs.