Modulation of The Condensate Conformation and Interaction for Drug Discovery

CD BioSciences offers a variety of condensate-based drug discovery strategies to achieve repair condensatopathy, disrupt the normal function of condensates associated with disease, and prevent targets from acting by disabling them in their natural condensates or by separating them from their natural condensates. Here, we help you with drug development by modulating the condensate conformation and interaction.

Introduction of Protein Conformation in Biomolecular Condensates

Protein conformations are generated by a complex interaction of physicochemical forces acting on protein and solvent atoms. Studies have shown that biomolecular condensates driven by multivalent intermolecular interactions are mediated by ordered-disordered transitions in protein conformation and protein structural domains. In most cases, the main driving force for biomolecular condensate formation is the intermolecular affinity of intrinsically disordered proteins (IDPs). Conformational dynamics and interactions within biomolecular condensates play a critical role in their formation and function. Understanding the regulation of condensate conformational states and intermolecular interactions is important for drug discovery, as it opens new avenues for targeting proteins associated with condensates in various disease states.

The current challenges in regulating condensate conformation and interactions face the following:

• The inherent conformational flexibility of intrinsically disordered regions (IDRs) within proteins makes it difficult to target them using traditional structure-based approaches. The dynamic nature of IDRs requires the development of innovative methods to screen and design molecules that interact with these regions.
• The complex interactions of molecular interactions within the condensate require a detailed understanding of the underlying mechanisms to identify potential points of intervention.

Fig. 1. Protein conformation and biomolecular condensates. (Vazquez DS, et al, 2022)

Our Solutions

CD BioSciences is committed to modulating the condensate conformation and interaction landscape to develop strategies for drug discovery. By targeting specific conformational states in condensates, we aim to influence the behavior of proteins associated with condensates by facilitating or inhibiting interactions with other biomolecules.

We provide innovative solutions for modulating the conformational and interaction landscape of condensates. Our experts draw on expertise in protein engineering and computational biology to develop a multidisciplinary approach to identify and localize specific conformational states in biomolecular condensates.

• Rational Design of Condensate-Modifying Therapeutics
  We employ a rational design strategy to develop condensate-modifying therapeutics for molecules that interact with the IDR of condensate-associated proteins. We aim to design condensate-modifying therapeutics that selectively modulate the conformational state of proteins to alter their ability to partition into condensates or to prevent proteins from forming various intermolecular interactions with other biomolecules within the condensate.
• High-Throughput Screening Technologies
  We offer high-throughput screening techniques (e.g. fragment-based screening and virtual screening) to identify potential candidates for condensate-modifying therapeutics. These methods enable rapid screening of large chemical libraries to identify molecules with the desired binding affinity and specificity for the target IDR. By using computational algorithms and molecular modeling, we can also predict binding interactions between condensate-modifying therapeutics and IDRs to help select promising drug candidates for further development.
• Validation and Optimization of Condensate-Modifying Therapeutics
  Once potential candidates have been identified, we employ a rigorous validation and optimization process. This involves comprehensive biophysical and biochemical characterization of condensate-modifying therapeutics-protein interactions, including assays to assess binding affinity, specificity, and selectivity.
• In Vitro and In Vivo Studies
  CD BioSciences has conducted extensive in vitro and in vivo studies to evaluate the therapeutic potential of the developed condensate-modifying therapeutics. In vitro studies involve testing condensate-modifying therapeutics in relevant cellular models to assess their effects on condensate formation, protein-protein interactions, and cellular processes associated with the target disease. In vivo studies use animal models to investigate the pharmacokinetics, safety, and efficacy of condensate-modifying therapeutics.

CD BioSciences provides innovative solutions for condensate conformation and interaction drug development through rational condensate-modifying therapeutics design, high-throughput screening technologies, and a comprehensive validation and optimization process. Our solutions can provide new ways to target proteins associated with biomolecular condensates. If you are interested in our solutions, please contact us now to seize new drug development opportunities.