The challenge in early drug discovery is not just finding molecules that bind but finding novel chemical matter that expands beyond crowded IP space and traditional scaffolds. Most high-throughput or biophysics-only screens identify hits indirectly and often miss unconventional binders.
SmartSoak® Screening changes this. By applying crystallography at the very start in the context of fragment-based drug discovery, fragment binding is observed directly in protein structures. This “crystal structure first” paradigm provides unambiguous 3D data for each hit, ensuring medicinal chemistry starts from validated binding modes rather than assumptions.
From kinase programs to protein–protein interaction targets, SmartSoak® has demonstrated the ability to uncover unexpected binding modalities, new scaffold classes, and even induce conformational changes that open hidden pockets.
Direct structural validation — Every fragment hit is structurally confirmed, removing uncertainty and reducing false positives.
Novel chemotypes — SmartSoak® hits consistently expand chemical space with scaffolds not represented among known binders.
Chemical space docking integration — Validated fragment structures can be directly used as seeds for large-scale docking of chemical space sampling billions of follow up molecules to accelerate from fragment to potent hits.
Revealing new sites and conformations — Screens not only identify active site binders but also uncover binding at allosteric and peripheral sites.
Relevance for advanced modalities — Structurally defined hits with multiple exit vectors are particularly valuable for the design of PROTACs and molecular glues, where ternary-complex geometry is key.
Direct structural validation — Every fragment hit is structurally confirmed, removing uncertainty and reducing false positives.
Novel chemotypes — SmartSoak® hits consistently expand chemical space with scaffolds not represented among known binders.
Chemical space docking integration — Validated fragment structures can be directly used as seeds for large-scale docking of chemical space sampling billions of follow up molecules to accelerate from fragment to potent hits.
Revealing new sites and conformations — Screens not only identify active site binders but also uncover binding at allosteric and peripheral sites.
Relevance for advanced modalities — Structurally defined hits with multiple exit vectors are particularly valuable for the design of PROTACs and molecular glues, where ternary-complex geometry is key.
Because SmartSoak® gives direct structural proof of binding. This avoids false positives from assay artifacts and ensures medicinal chemistry begins with confidence.
Fragment hits often represent novel chemotypes, and frequently explore underrepresented chemical space. They provide fresh IP opportunities and stronger differentiation.
Each fragment structure serves as a seed for virtual fragment evolution using Chemical Space Docking and FragAI, enabling efficient exploration of chemical spaces. This expands fragments into potent, drug-like hits in just one or two design cycles.
Yes. Beyond canonical active sites, SmartSoak® screening routinely reveals allosteric and hidden binding sites and can capture ligand-induced conformational changes that open new druggable pockets.
Because these modalities depend on precise structural geometry of ternary complexes. SmartSoak® hits provide exit vectors and conformational detail that guide rational design of bifunctional molecules.
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