Explicit Ions for Coarse-Grained Simulations of Intrinsically Disordered Proteins via Hydrophobicity/Hydrophilicity Scales

Abstract

Intrinsically disordered proteins (IDPs) play a role in many different biological functions, such as molecular signaling or formation of membraneless organelles. A common method for studying IDPs is coarse-grained simulations due to large length and timescales that must be probed to simulate phenomena of interest. Many IDPs are highly charged and can have strong interactions with ions in solution. While most coarse-grained simulations rely on screened electrostatics interactions inspired by Debye-Huckel theory to implicitly capture the effect of ions on, implicit ions are ineffective in properly capturing the effects of the variation of ionic strength and Hofmeister effects, as well as the entropic contribution from ion release on binding. In order to better capture these effects, we have developed explicit ions for inclusion in the otherwise implicit solvent, hydrophobicity scale coarse-grained model for implicitly disordered proteins. Explicit ions are modeled by taking advantage of a hydrophilicity scale, which allows for the modification of the attractive part of the non-bonded interaction without modifying the excluded volume. The hydrophilicity parameter of a series of ions is parameterized by matching chain properties of a set of IDPs in a solution of a variety of ions. The hydrophilicity is then related to the free energy of hydration to predict parameters ions not in the parameterization set. The change in upper critical solution temperature as a function of ion type and ionic strength is also investigated, and related to experiment.