Multiscale Modeling Service for Protein-RNA Condensation

Biomolecular condensates consist of relatively dense proteins and nucleic acids. Multivalent interactions, the presence of conformationally flexible molecules, and electrostatic interactions between highly charged molecules are key factors that facilitate the phase separation of biomolecular condensates. In biological environments, RNA has been found to play an important role in condensation formation due to its electrical charge. Protein-RNA condensation is closely related to biological functions such as transcription, translation and RNA metabolism in cells. However, studying the biophysical properties of protein-RNA condensates is limited, mainly due to the molecular heterogeneity and conformational flexibility of RNA and protein chains, as well as the non-equilibrium nature of the transcriptional and cellular environments. Many methods using both physics-based and computer-based approaches have been developed at multiple granularities to model protein and RNA condensation.

Fig. 1. A hierarchy of multiscale models which have been used for studying protein-RNA condensation. (Laghmach R, et al., 2022)

Customized Services

Modeling the folding and assembly of biomolecular condensates is challenging due to their large size and long time scales. We develop many methods to reduce computational costs by coarsening the granularity of the problem. We help you analyze the cohesion between negatively charged RNA and positively charged proteins without the polymeric characteristics or specific binding interactions of each component.

Based on advanced computer simulation, bioinformatics and mathematical modeling platforms, CD BioSciences offers multi-scale computer simulation combined with microscopy and spectroscopy experiments to characterize the phase separation of mixtures of RNA and proteins. Our innovative models validate experimental observations in a comprehensive and physically based manner.

Multiscale Modeling of Protein Structure and Dynamics

Modeling proteins is difficult due to the wide range of lengths and time spans. We offer multiscale approaches to model protein structure and dynamics by performing coarse-grained processing in either the length domain or the time domain. Different length scale resolutions are mixed in a sequential or parallel manner at the length scale. At the time scale long time scale dynamics are predicted by constructing short atomic simulation models, effectively coarsening in the time domain.

RNA Modeling

Our RNA staff responds to the physicochemical differences between RNA and proteins by developing computational tools that differ in many respects from those dealing with proteins. We offer both strategies to model RNA dynamics by limiting fine-grained calculations to selected regions and by reducing the power granularity of the entire system. In addition, we provide fragments extracted from structural databases to assemble molecules and to predict and evaluate RNA structure.

Multiscale Modeling of Protein-RNA Condensation

We provide atomic and coarse-grained molecular-based models, and field-theoretical models to analyze the biophysical properties of protein-RNA condensates.

• All-Atom and Coarse-Grained Resolution Models of Protein-RNA Condensation
  We provide atomic simulations to study protein-RNA interactions in condensates in detail. Due to the multi-scale nature of biomolecular condensates, we employ resolutions designed to capture scales relevant to predicting thermodynamic and kinetic phenomena, including critical temperatures, double junction lines, interfacial tensions, surface fluctuations, etc.
• Field-Theoretic Models of Protein-RNA Condensation
  We provide field theory models to study the equilibrium and nonequilibrium aspects of phase separation of biomolecular condensates at the mesoscopic scale, particularly protein and RNA condensation. We can quickly help you analyze the complex interactions of protein and RNA coalescence driving forces, focusing only on the basic thermodynamics of component interactions.

Our Theoretical/Computational Approaches

• Analytical theory.
• Field theory simulations.
• Lattice models.
• All-atom and coarse-grained simulations.

Our computer simulations of RNA and protein phase separation are subsequently supported by experimental validation with microscopy and spectroscopic experiments. 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.