Calculation of Binodals and Interfacial Tension of Phase-Separated Condensates
Biomolecular condensates formed by liquid-liquid phase separation are revolutionizing scientists' understanding of biology. Although phase separation of intrinsically disordered proteins (IDPs) is a physical phenomenon associated with many fundamental cellular processes, there is a growing gap between the biology and physics of condensates. A number of theoretical models have been measured for structured and disordered proteins. Phase separation occurs through two mechanisms, including the process of spinodal disassembly and the generation of nuclei. However, a robust approach to calculate the binodals from molecular dynamics simulations of IDPs modeled at the all-atomic level in explicit solvents remains elusive because of the difficulty in preparing the appropriate initial dense conformation and achieving phase equilibrium.
Fig. 1. Computing binodals and interfacial tension of biomolecular condensates from simulations of spinodal decomposition by SpiDec. (Mazarakos K, et al., 2022)
Customized Services
Biomolecular condensates are homogeneous, dense phase coexisting with a surrounding dilute phase. The dependence of density on temperature in the two phases is called binodals, and the difference in density and intermolecular interactions create interfacial tension. Our expert team calculates the binodals by designing different paths to satisfy equality between the two phases in terms of temperature, pressure and chemical potential.
Based on our advanced computational platform and strong expertise in liquid-liquid phase separation biophysics, CD BioSciences offers a variety of molecular simulation methods to calculate binodals and interfacial tensions for phase separation condensates.
- Classical Plate Method
We offer the classical flat-plate method to calculate binodal nodes for a variety of coarse-grained models of biomolecular condensates, from spherical particles and homopolymers to residue-level models for IDPs to per-residue multibead models for dipeptides.
- Fourier Transform-Based Modeling of Atomistic Protein-Protein Interactions
Our method uses Fast Fourier Transforms to calculate the chemical potential of protein solutions and protein binodes modelled at the all-atom level in implicit solvents instead of IDPs.
- Slab-Geometry Molecular Dynamics Simulation
We offer this approach to perform full simulations at the coarse-grained level and then map to atomic systems, from point particles to proteins in explicit solvents. This all-atomic level simulation allows predicting the matching effects of biomolecular condensates on critical temperature and interfacial tension. In addition, coarse-grained simulations allow predicting the sequence dependence of intrinsically disordered protein phase equilibria.
※ It should be noted that this approach does not achieve equilibrium between phases.
- Gibbs-ensemble Monte Carlo Simulation
We offer the Gibbs-ensemble Monte Carlo method to analyze phase equilibria of biomolecular condensates and complex condensates to help customers gain insight into biomolecular condensates and complex condensed layers, especially due to the difficulty of inserting polymer chains into dense solutions.
※ It is important to note that this method cannot be applied to all-atom models.
Advantages of Three Molecular Simulation Methods
- Fast Fourier transform method models phase-separated protein molecules in atomic detail, allowing the effect of individual amino acids on phase equilibrium to be studied.
- Gibbs-ensemble Monte Carlo method allows the use of relatively small system sizes to obtain computational efficiency.
- Slab-geometry molecular dynamics simulation is applicable to atomic mechanics proteins in explicit solvents, allowing calculation of interfacial tensions.
CD BioSciences is committed to providing our customers with professional services for the calculation of binodals and interfacial tensions of phase separated condensates. Our scientists continue to search for ways to both accurately model the system and quickly achieve phase equilibrium. We aim to accelerate your physical understanding of biomolecular condensates through computational simulations and to stimulate experimental validation. If you have any special requirements for our services, please feel free to contact us. We are looking forward to working together with your attractive projects.
