(553b) Effect of Therapeutic Molecules on Phase Separation and Dynamics of Intrinsically Disordered Proteins

Membrane-less organelles are liquid-like droplets formed by the liquid-liquid phase separation (LLPS) of biomacromolecules in cells. Failure in LLPS was found to be highly correlated with infertility and diseases. Besides, the loss of liquid-like behaviors, being gelation or solidification, results in neurological disorders. Developing therapeutic molecules is attracting lots of attention with the goal of tailoring the LLPS and the dynamic properties of the membrane-less organelles. Here, we investigated the effects of amino acids, as small therapeutic molecules, on the phase separation and dynamics of proteins. We focused on widely studied intrinsically disordered proteins, LAF-1 and FUS. Twenty different amino acids and their concentrations varied in LAF-1 and FUS systems. We determined their critical phase separation temperature and the diffusivity of LAF-1 and FUS molecules in the condensate phase if phase separation occurred. This study will provide guidelines for the design of therapeutic molecules to modulate the phase separation process of biomolecules forming membrane-less organelles as well as their dynamics in the condensate phase.