Mechanistic Insights on ATP's role as Hydrotrope

Abstract

Hydrotropes are small amphiphilic molecules which help in solubilizing hydrophobic entities in aqueous medium. Recent experimental investigation has provided convincing evidences that, adenosine triphosphate (ATP), besides being an energy currency of cell, also can act as hydrotrope to inhibit the formation of protein condensates. In this work, we have designed computer simulations of prototypical macromolecules in aqueous ATP solution to dissect the molecular mechanism underlying ATPs newly discovered role as a hydrotrope. The simulation demonstrates that ATP can unfold a single-chain of hydrophobic macromolecule as well as can disrupt the aggregation process of a hydrophobic assembly. Moreover, the introduction of charges in the macromolecule is found to reinforce ATPs disaggregation effects in a synergistic fashion, a behaviour reminiscent of recent experimental observation of pronounced hydrotropic action of ATP in intrinsically disordered proteins. A molecular analysis indicates that this new-found ability of ATP are ingrained in its propensity of preferential binding to the polymer surface, which gets fortified in presence of charges. The investigation also renders evidence that the key to the ATPs superior hydrotropic role over chemical hydrotrope (Sodium xylene sulfonate, NaXS) may lie in its inherent self-aggregation propensity. Overall, via employing a bottom-up approach the current investigation provides fresh mechanistic insights into the dual solubilizing and denaturing abilities of ATP.