Our ReSOLVETM drug discovery platform integrates our structural biology and protein science expertise with our proprietary computational chemistry capabilities to address the current limitations of small molecule drug discovery: finding promising binding pockets in proteins that adopt many transient conformations and designing small molecules that bind selectively to those pockets. We are thus able to identify new drug molecules for targets which have never been drugged, or for which existing chemical matter leaves significant room for improvement.

We are continuously searching for new ReSOLVE targets, and are interested in discussing collaboration opportunities with potential partners. If you are interested in learning more about ReSOLVE, please contact us.

THE HYDROCOPHORE:
a “blueprint” for
small molecule design

 

The hydrocophores are the solvation structures of the binding pockets on a protein target. With ReSOLVE, we can extract the hydrocophores and use them as blueprints for the design of small molecules. ReSOLVE allows us to understand the shape, polarity, and potential druggability of binding pockets at a new level of resolution.

Efficient virtual screens that generate
NOVEL CHEMICAL MATTER

 

The hydrocophore enables virtual screening of libraries of billions of compounds. The output is a prioritized set of small molecules with a high probability of binding efficiently to the screened pocket. We then pursue wet-lab testing of only a limited number of compounds (on the order of dozens), thus reducing cost and time involved in testing potential hits and optimizing promising chemical matter and improving our overall efficiency.

A New Level of
Resolution with
ReSOLVE

 

Protein science expertise: Highly enabled structure-based drug design

High-quality protein target structural information is required to fully take advantage of our unique unrestrained molecular dynamics and solvation analysis tools.

Ventus has deep in-house expertise in protein engineering, expression, and structure determination. This has allowed us to solve high-resolution structures of challenging targets such as NLRP3 and cGAS and proceed to structure-based drug design.

We can effectively apply ReSOLVE to experimentally determined structures that we solve internally, as well as refine computationally predicted protein structures.

 

Unrestrained molecular dynamics: Modeling and clustering a moving protein’s many conformations

Computer simulations of proteins in motion produce millions of conformations for evaluation. Many existing conformation clustering methods result in configurations that don’t exist in nature and will lead to a dead-end in the drug discovery process.

ReSOLVE enables the unbiased modeling of a broad set of configurations for a dynamic protein, including those that are rare, addressing this limitation.

 

Accurate modeling of the dynamic solvation structure of binding pockets  

Traditional methods to identify small molecules that can bind to pockets on proteins are not designed to account for the importance of the dynamic nature of the solvation structure within a binding pocket.

ReSOLVE addresses this limitation by modeling the dynamic solvation structure of each conformation to identify hydrocophores, three-dimensional blueprints of existing pockets.

The ReSOLVE platform enables drug discovery by leveraging the hydrocophore:
  • High resolution protein structures
  • Novel conformations of dynamic proteins
  • Accurate modeling of the solvation structure of a binding pocket
  • Efficient virtual screening of massive libraries
  • Identification of novel chemical matter
  • Reduction in time and cost over traditional methods