Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

40-POS Board 40 GTP IS A BETTER HYDROTROPE THAN ATP Mayank P. Pandey 1 ; Sreeja Sasidharan 2 ; V A Raghunathan 2 ; Himanshu Khandelia 1 ; 1 University of Southern Denmark, Odense, Denmark 2 Raman Research Institute, Bangalore, India Hydrotropes are small amphiphilic compounds that increase the aqueous solubility of hydrophobic molecules. Recent evidence suggests that adenosine triphosphate (ATP), which is the primary energy carrier in cells, also assumes hydrotropic properties to prevent the aggregation of hydrophobic proteins. Here, we show that guanosine triphosphate (GTP) has superior hydrotropic properties than all other nucleoside triphosphates (NTPs). We compare the hydrotropic behaviour of all four biological NTPs using molecular dynamics (MD) simulations. We launch all-atom MD simulations of aqueous solutions of NTPs (ATP, GTP, CTP and UTP) with pyrene, which acts both as a model hydrophobic compound, and a spectroscopic reporter for aggregation. GTP prevents pyrene aggregation and dissolves pre-formed pyrene clusters effectively. Dissolution is not achieved in the presence of CTP and UTP. The higher stability of base stacking in guanine is responsible for the higher hydrotropic efficiency of GTP. Consistent with the simulations, spectroscopic measurements also suggests that the hydrotropic activity of GTP is higher than ATP. Our results can have broad implications for hydrotrope design in the pharmaceutical industry, as well as the possibility of cells employing GTP as a hydrotrope to regulate hydrophobic protein aggregation in membrane-less biological condensates.

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