In silico prediction of in vitro protein liquid-liquid phase separation experiments outcomes with multi-head neural attention

Abstract

Motivation: Proteins able to undergo liquid-liquid phase separation (LLPS) in vivo and in vitro are drawing a lot of interest, due to their functional relevance for cell life. Nevertheless, the proteome-scale experimental screening of these proteins seems unfeasible, because besides being expensive and time-consuming, LLPS is heavily influenced by multiple environmental conditions such as concentration, pH and temperature, thus requiring a combinatorial number of experiments for each protein. Results: To overcome this problem, we propose a neural network model able to predict the LLPS behavior of proteins given specified experimental conditions, effectively predicting the outcome of in vitro experiments. Our model can be used to rapidly screen proteins and experimental conditions searching for LLPS, thus reducing the search space that needs to be covered experimentally. We experimentally validate Droppler's prediction on the TAR DNAbinding protein in different experimental conditions, showing the consistency of its predictions.