Conformational genetics is the engine we use at Roivant Discovery 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 that a particular amino acid residue of a protein is implicated in a disease, but genetics does not say why it is important. To get the answers about “why”, we run molecular simulations to understand the conformational mechanism (i.e. how the mutation alters the dynamic shape of the protein target) 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 molecular simulations, the team at Roivant Discovery 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 an understanding of the free energy landscape can be leverage to design therapeutic molecules at an atomistic level. We compare our predictions 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.