NK2R (neurokinin 2 receptor) is a G protein-coupled receptor closely tied to metabolic regulation. Much of the attention it has drawn stems from its distinctive dual mode of action: in the central nervous system, NK2R activation is linked to appetite control, whereas in peripheral tissues it is associated with increased energy expenditure. Its endogenous ligand, NKA (neurokinin A), is able to activate the receptor, but native peptides make poor drug molecules — they are short-lived in circulation and raise problems of receptor selectivity.

In the experimental testing already completed for the 2025 Peptide Design Competition, the most potent entry reached an EC50 of 2 nM, exceeding that of the natural peptide NKA. From sequence generation and structure prediction through to actual chemical synthesis and functional assays, a cohort of in silico designs was put to the test at the bench for the first time, showing that AI-designed molecules can genuinely work.

The competition imposes no restriction on binding sites and prescribes no particular design route, and no entry is rewarded or penalized according to its mechanism of action. Each participant submits three candidate nanobody sequences, and the three must be independent designs, distinct from one another.

Basic requirements

• Sequence type: nanobody

• Sequence length: 100–150 aa for the full-length construct

• Framework region: origin and sequence unrestricted

Please note

• The competition includes no second round of optimization based on experimental results. Sequences shall not be replaced or supplemented after the submission deadline.

• The organizing committee will first conduct structure prediction of the nanobody bound to NK2R and Gα in its activated state (Protein sequences: NK2R, Gα) using AlphaFold3. The ipTM (interface predicted TM-score) of nanobody and NK2R above 0.6 are carried forward. The qualifying entries are then ranked by ΔSASA (the change in solvent-accessible surface area), and the top 300 sequences are selected.

• Team entries are encouraged: if none of the sequences submitted by a team of three or more participants is selected, the team may nominate one sequence to proceed to the synthesis and testing stage. Candidate sequences that advance to experimental testing will undergo activity assays, and the final ranking will be determined by the experimental results.

• Please pay special attention: all sequences and data submitted in this competition will be open for sharing and can be used by others free of charge.

• 24 September to 11 November 2026, 24:00 (UTC+8) - Registration and sequence submission

• 11 November 2026 to 31 March 2027, 24:00 (UTC+8) - Synthesis and testing

• April 2027 - Final results announcement and award ceremony

You may add our official WeChat account (FRCBS-THU) to gain access to the competition discussion group.