In Silico View of Crowding: Biomolecular Processes to Nanomaterial Design

It is widely accepted that deciphering biomolecular structure and function requires going beyond the single-molecule or single-complex paradigm. The densely packed macromolecules, cosolutes, and metabolites in the living cell impose crowding effects on the biomolecular structure and dynamics that need to be accounted for. Molecular simulations have proven to be a powerful tool to advance the current molecular-level understanding of such a highly concentrated, complex milieu. This Mini-Review focuses on summarizing the understanding achieved so far for the effects of crowding on biomolecular processes using computational methods, along with highlighting a new direction in employing crowding as a tool for tunable nanomaterial design. The two schools of thought that form the pillars of the current understanding of crowding effects are discussed. The investigation of crowded solutions using physics-based models that encompass different time and length scales to mimic the intracellular environment are described. The limitations and challenges faced by the current models and simulation methods are addressed, highlighting the gaps to be filled for better agreement with experiments. Crowding can also act as an effective tool to modulate the structure-property-function relationships of nanomaterials, leading to the development of novel functional materials. A few recent studies, mostly experimental, have been summarized in this direction. The Mini-Review concludes with an outlook for future developments in this field in order to enable accurate mimicking of the intracellular environment using simulations and to bridge the gap between biological processes and nanomaterial design.