Recent Progress in Modeling and Simulation of Biomolecular Crowding and Condensation Inside Cells.

Area of Science:

• Biophysics
• Computational Biology
• Cellular Biology

Background:

• Macromolecular crowding in the cytoplasm influences protein diffusion, stability, binding, organization, and phase separation.
• The precise molecular mechanisms driving crowding's effects on macromolecular dynamics and conformations remain incompletely understood.

Purpose of the Study:

• To review physics-based and data-driven computational methods for studying macromolecular crowding and intracellular protein condensation.
• To highlight recent advancements in modeling and simulation of biomolecular systems from single molecules to the entire cytoplasm.

Main Methods:

• Focus on computational approaches, including physics-based and data-driven methods.
• Review of modeling and simulation techniques applied to biomolecular systems of various scales.
• Analysis of phenomena influenced by macromolecular crowding.

Main Results:

• Computational methods provide high-resolution insights into macromolecular crowding effects, complementing experimental techniques.
• Discussion of crowding's impact on diffusion, protein-ligand binding, and condensate properties like surface tension.
• Overview of progress in simulating diverse biomolecular systems.

Conclusions:

• Computational tools are crucial for elucidating macromolecular crowding's role in cellular function.
• Further development is needed to accurately model in vivo conditions and address outstanding challenges in cellular simulations.