Liquid-liquid phase separation (LLPS) is a process that results in the formation of a polymer-rich liquid phase coexisting with a polymer-depleted liquid phase. In the context of highly complex phase separation systems, atomic simulations using quantum mechanics or atomic molecular dynamics (MD) are often severely limited within a given computational budget. Based on our continuous improvements in computer performance and extensive experience in theoretical and experimental studies, CD BioSciences offers particle-based theoretical simulation services for liquid-liquid phase separations by applying different coarse-grained levels to reproduce experiments and obtain various statistical properties.

To reduce the complexity of particle-based simulations, our experts construct and select appropriate coarse-grained methods to efficiently perform multiple computer simulations with different condition settings, providing you with a global picture of the parameter space and guiding experiments. CD BioSciences offers a customized process for particle-based simulation for particle-based simulation of liquid-liquid phase separations.

(1) Setting System Conditions

We set the system conditions for LLPS simulations by selecting appropriate simulation units, sizes, boundary conditions and kinetic equations for atomic and molecular dynamics simulations.

(2) Set Up the Coarse-Grained Model

Coarse-grained levels may vary from residue-based to whole macromolecules. We will build the appropriate coarse-grained model based on the customer's specific requirements. We offer different coarse-graining methods to build multi-scale models that can highlight charge effects between residues and reflect the flexibility of disordered regions. In addition, we can implement further coarse-grained models based on specific time and length scales.

(3) Generate initial configurations of multiple molecules in the simulation box to achieve target concentrations.

(4) Identify Key Interactions and Parameterizations

Among the many interatomic potentials present in the cellular environment, we help you identify the fundamental physical variants leading to LLPS, including exclusive volume effects between all particle pairs, bonding interactions, hydrophobic interactions, etc.

(5) Run the Simulation

Preheat the system to avoid extremely unreasonable initial configurations, and then run certain steps until the system reaches equilibrium.

(6) Constructing Phase Diagrams

We provide a very effective strategy for the simulation of intrinsically disordered proteins to construct temperature-concentration phase diagrams. This phase diagram provides the basis for LLPS experiments. In addition, by merging phase diagrams of different biological systems, we can also fully explain how mutations, PTM, different charge patterns or chemical properties affect the phase separation ability.

(7) Acquisition of Trajectories and Analysis of Simulation Results

In addition to phase diagrams, our simulation results provide any desired statistical properties at simulation resolution, including thermodynamic properties such as energy and pressure, as well as dynamic information about cluster growth, droplet fusion, and molecular mean square displacement (MSD).

Advantages of the Particle-Based Theoretical Simulation Method

• Parameters and potentials for coarse-grained simulations are obtained at the atomic level by calculating microscopic interactions and spatial effects.
• Different coarse-grained levels are applied to reproduce the experiments and to obtain various statistical properties.
• An efficient simulation strategy.
• Obtain phase diagrams and explore phase behavior based on phenomenological theory.
• Determine parameter dependence and predictability.

CD BioSciences is the ideal partner for your research in liquid-liquid phase separation biophysics. We will be happy to discuss the details of your interaction study, and develop an experimental approach based on your requirements. If you are interested in our services, please do not hesitate to contact us for more information.