Harnessing biomolecular motion to design novel therapeutics that precisely reprogram protein function

Expand the boundaries of
drug discovery

Target insights

Modeling biomolecular motion uncovers novel therapeutic approaches

Considering the dynamic behavior of proteins expands the design space of therapeutics. Here, we simulate the dynamic protein-protein interface to pinpoint optimal strategies for designing molecules that maximize the intended conformational and therapeutic effect.

Generative design

Computational models generate diverse molecular designs aligned with the therapeutic hypothesis

Here, we search the design space for molecular glues that will reprogram protein function by stabilizing the desired protein-protein interface.

Computational assay

Predictive models enable accurate and high-throughput evaluation of therapeutic potency of molecular designs

Computational models forecast not only the affinities of the designed molecules for the target proteins but also their effects on functions. Here, we interrogate the efficacy of therapeutic degraders in tagging a protein for degradation. The therapeutic degraders induce transfer of ubiquitin to the surface lysines on the target protein.

CASE STUDY 01
Computation-driven optimization of mutant KRAS inhibitors

Accelerating discovery

Accurate binding affinity predictions speed up drug discovery
Consideration of binding pocket flexibility achieved valuable target insights leading to highly accurate predictions of molecular binding
Our binding free (BFE) energy calculations enabled discovery of twice as many bioactive molecules from half as many synthesized.
Target insights
Elucidation of multiple pocket conformations
Generative design
Autonomous generation of hundreds of pocket-compatible molecular designs
Computational assay
Prediction of KRAS inhibition
CASE STUDY 02
SMARCA2 degrader design based on novel protein-protein interfaces

Expanding the design space

The first successful design of potent degraders based on computationally modeled protein-protein interfaces