Conformational Genetics

Conformational genetics is the engine we use at Silicon Therapeutics for selecting targets and defining our design strategy.  The relationship between human disease genetics and the associated conformational mechanism that influences pathway signaling informs about us how to design drugs that appropriately modulate the target for therapeutic effect.

Making Human Disease Genetics Actionable for Drug Design

From What to Why

Biology and human genetics tell us what is important about a particular amino acid residue implicated in a disease, but genetics does not say why it’s important. To get the answers about why a mutation is important in a disease, we run molecular simulations to understand the conformational mechanism and devise a molecular design strategy to modulate the conformation in a way to treat the underlying disease.

From these atomistic insights derived from quantum mechanics, statistical thermodynamics, and simulations, the team at Silicon Therapeutics develops hypotheses regarding the conformational mechanism of action and the “druggability” of the target. Based on the data that flow from our hypotheses, our scientists develop a research strategy to better understand how the free energies work at an atomistic level. We then compare our new understanding of the protein conformational mechanism of action with genetic data to further validate our hypotheses. Once we understand how the protein system works, we can chart our path forward for drug design on an atom-by-atom level.