One-Step Protein Half-Life Estimation from Irreversible Inhibition and Degradation Time Courses

Abstract The half-life of proteins plays a pivotal role in understanding their stability, turnover rate, and functional lifespan within a cell. In this work, we analyze the turnover equation for irreversible protein modifications, such as those occurring during covalent inhibition and targeted protein degradation by PROTACs or molecular glue degraders. Based on this analysis, we introduce a formula for straightforwardly determining protein half-life directly from the time course of unmodified protein. This approach offers a practical and efficient alternative for estimating half-lives, complementing existing techniques and potentially enhancing their applicability across diverse experimental settings.