Investigation of the effect of macromolecular crowding on the biomolecular condensation of globular proteins and their functional aspects

Abstract

Macromolecular crowding in the cytosol of the eukaryotic cell profoundly influences the conformational dynamics and intermolecular interactions of biological macromolecules, driving diverse behaviours such as liquid–liquid phase separation (LLPS), protein aggregation, and modulation of enzymatic activity [1, 2]. Despite its importance, the role of crowding in regulating the phase behaviour and functionality of globular proteins remains poorly understood. In this thesis, we provide an integrated analysis of the impact of macromolecular crowding on the LLPS, conformational dynamics, and functional stability of three functional proteins human serum albumin (HSA), human serum transferrin (Tf), and trypsin-like serine proteases, highlighting the underlying mechanisms and potential physiological and biotechnological implications.