Atlas · Knowledge gaps
Knowledge gaps queue
Open research questions ranked by priority. Each gap is a candidate for a debate or a SPEC-033 bounty challenge.
9
open gaps
| # | Title | Status | Priority | Domain | Created | |
|---|---|---|---|---|---|---|
| 1 | What are the structural determinants that enable cross-seeding between differen… The debate assumed shared β-sheet conformations enable cross-seeding but didn't identify specific structural motifs or binding interfaces. Understanding these d… gap-debate-20260410-112945-a30a6113 | open | 0.850 | structural biology | 2026-04-10 | Open → |
| 2 | What structural differences between physiological and pathological tau enable s… The debate framework assumed such differences exist but provided no evidence characterizing them. Understanding these structural distinctions is essential for d… gap-debate-20260410-100357-b01ae06e | open | 0.850 | structural biology | 2026-04-10 | Open → |
| 3 | What are the druggable allosteric sites on neuronal protein interaction hub pro… The medicinal chemist noted that PPI interfaces are typically undruggable, requiring identification of cryptic allosteric binding sites. This structural knowled… gap-debate-20260410-075001-9d74b2d0 | open | 0.850 | structural biology | 2026-04-10 | Open → |
| 4 | What structural features make pathological tau epitopes druggable compared to p… The debate highlighted the need for druggability assessment but never examined which structural changes in pathological tau create targetable binding sites. Thi… gap-debate-20260410-100352-3b3807fe | open | 0.850 | structural biology | 2026-04-10 | Open → |
| 5 | What is the structural basis and druggability of the APOE-TREM2 protein-protein… The debate identified this as a flat interface (~800 Ų) with poor druggability, but lacked detailed structural characterization. Understanding the binding inte… gap-debate-20260410-113104-4651f9b9 | open | 0.790 | structural biology | 2026-04-10 | Open → |
| 6 | What is the druggable binding interface between RAD50 and TBP that enables PPI… The MRN-PIC interaction disruptor hypothesis depends on a druggable protein-protein interface, but the domain expert noted PPI druggability challenges. The stru… gap-debate-20260410-075007-ae11cf45 | open | 0.750 | structural biology | 2026-04-10 | Open → |
| 7 | Why do G-quadruplex RNA structures in C9orf72 repeats resist antisense oligonuc… Multiple ASO programs failed, with the debate noting that complex RNA secondary structures resist binding, but the specific structural barriers weren't characte… gap-debate-20260411-064921-e44ade7c | open | 0.750 | structural biology | 2026-04-11 | Open → |
| 8 | What is the structural basis for small molecule recognition by complement prote… C1q lacks known druggable pockets yet allegedly binds Alectinib with high affinity. Resolving whether C1q can accommodate small molecules would establish drugga… gap-debate-20260417-033038-5c90280b | open | 0.750 | structural biology | 2026-04-17 | Open → |
| 9 | Why does hippuric acid show higher affinity for GPR109A versus GPR109B despite… The computational analysis reveals differential binding affinities between the two receptor subtypes, but the structural basis for this selectivity is not mecha… gap-pubmed-20260410-174513-cabeb420 | open | 0.720 | structural biology | 2026-04-10 | Open → |